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1
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Zhang K, Di G, Bai Y, Liu A, Bian W, Chen P. Aquaporin 5 in the eye: Expression, function, and roles in ocular diseases. Exp Eye Res 2023; 233:109557. [PMID: 37380095 DOI: 10.1016/j.exer.2023.109557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 05/26/2023] [Accepted: 06/25/2023] [Indexed: 06/30/2023]
Abstract
As a water channel protein, aquaporin 5 (AQP5) is essential for the maintenance of the normal physiological functions of ocular tissues. This review provides an overview of the expression and function of AQP5 in the eye and discusses their role in related eye diseases. Although AQP5 plays a vital role in ocular functions, such as maintaining corneal and lens transparency, regulating water movement, and maintaining homeostasis, some of its functions in ocular tissues are still unclear. Based on the key role of AQP5 in eye function, this review suggests that in the future, eye diseases may be treated by regulating the expression of aquaporin.
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Affiliation(s)
- Kaier Zhang
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, Shandong Province, China
| | - Guohu Di
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, Shandong Province, China
| | - Ying Bai
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, Shandong Province, China
| | - Anxu Liu
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, Shandong Province, China
| | - Wenhan Bian
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, Shandong Province, China
| | - Peng Chen
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, 266071, Shandong Province, China; Clinical Laboratory, Qingdao Central Hospital, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, 266042, Shandong Province, China.
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2
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Abstract
Sjögren's syndrome (SS) is a chronic autoimmune disease with the pathological hallmark of lymphoplasmacytic infiltration of exocrine glands - more specifically salivary and lacrimal glands - resulting in a diminished production of tears and saliva (sicca syndrome). The pathophysiology underscoring the mechanisms of the sicca symptoms in SS has still yet to be unraveled but recent advances have identified a cardinal role of aquaporin-5 (AQP5) as a key player in saliva secretion as well as salivary gland epithelial cell dysregulation. AQP5 expression and localization are significantly altered in salivary glands from patients and mice models of the disease, shedding light on a putative mechanism accounting for diminished salivary flow. Furthermore, aberrant expression and localization of AQP5 protein partners, such as prolactin-inducible protein and ezrin, may account for altered AQP5 localization in salivary glands from patients suffering from SS and are considered as new players in SS development. This review provides an overview of the role of AQP5 in SS salivary gland epithelial cell dysregulation, focusing on its trafficking and protein-protein interactions.
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3
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Wang L, Wang J, Zhu X, Bai C, Song Y. Aquaporins in Respiratory System. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1398:137-144. [PMID: 36717491 DOI: 10.1007/978-981-19-7415-1_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Aquaporins (AQPs) are water channel proteins facilitating fluid transport in alveolar space, airway humidification, pleural fluid absorption, and submucosal gland secretion. In this chapter, we mainly focus on the expression of four AQPs in the lungs, which include AQP1, AQP2, AQP4, and AQP5 in normal and disease status, and the experience of AQPs function from various model and transgenic mice were summarized in detail to improve our understanding of the role of AQPs in fluid balance of respiratory system. It has been suggested that AQPs play important roles in various physiology and pathophysiology conditions of different lung diseases. There still remains unclear the exact role of AQPs in lung diseases, and thus continuous efforts on elucidating the roles of AQPs in lung physiological and pathophysiological processes are warranted.
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Affiliation(s)
- Linlin Wang
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jian Wang
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaodan Zhu
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chunxue Bai
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuanlin Song
- Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
- Shanghai Key Laboratory of Lung Inflammation and Injury, Shanghai, China.
- Shanghai Institute of Infectious Disease and Biosecurity, Shanghai, China.
- Shanghai Respiratory Research Institute, Shanghai, China.
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
- Jinshan Hospital of Fudan University, Shanghai, China.
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4
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Expression Profiles of AQP3 and AQP4 in Lung Adenocarcinoma Samples Generated via Bronchoscopic Biopsies. J Clin Med 2022; 11:jcm11195954. [PMID: 36233821 PMCID: PMC9573329 DOI: 10.3390/jcm11195954] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/05/2022] [Accepted: 10/08/2022] [Indexed: 12/03/2022] Open
Abstract
Aquaporins (AQPs) are highly conserved channel proteins which are mainly responsible for the exchange of water and small molecules and have shown to play a pivotal role in the development and progression of cancer. Lung adenocarcinoma is the most common primary lung cancer seen in patients in Europe and the United States. However, in patients it is often not diagnosed until the advanced tumor stage is present. Previous studies provided strong evidence that some members of the AQP family could serve as clinical biomarkers for different diseases. Therefore, we aimed to investigate how AQP3 and AQP4 protein expression in lung adenocarcinoma (ADC) biopsy samples correlate with clinical and pathological parameters. The protein expression of AQP3 and AQP4 was analyzed based on immunohistochemical staining. AQP3 protein was observed in the cytoplasmic membrane of cancer tissue in 82% of lung samples. Significant differences in relative protein expression of AQP3 were noted between advanced age patients compared to younger counterparts (p = 0.017). A high expression of AQP3 was significant in cancer tissue when compared to the control group (p < 0.001), whereas a low AQP4 membrane expression was noted as significantly common in cancer tissue compared to non-neoplastic lung tissue (p < 0.001). Moreover, a low AQP4 membrane expression was positively correlated with a more advanced disease status, e.g., lymph node metastases (p = 0.046). Based on our findings, AQP3 and AQP4 could be used as biomarkers in ADC patients.
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5
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Ruscogenin Ameliorated Sjögren's Syndrome by Inhibiting NLRP3 Inflammasome Activation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:6425121. [PMID: 35800007 PMCID: PMC9256408 DOI: 10.1155/2022/6425121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 04/04/2022] [Indexed: 12/22/2022]
Abstract
This article investigated the role and the specific mechanism of Ruscogenin in Sjögren's syndrome (SS). NOD/ShiLtJ mice were treated with Ruscogenin, and acinar cells isolated from submandibular glands were treated with TNF-α, Ruscogenin and transfected with NLRP3 overexpression plasmid. Salivary flow rate (SFR) was measured at weeks 11, 13, 15, 17, and 20. Histological analysis of the submandibular glands was conducted by hematoxylin-eosin staining assay. IL-6, IL-17, TNF-α, and IL-1β mRNA expression was detected through qRT-PCR. AQP 5, AQP 4, P2X7R, NLRP3, caspase 1, IL-1β, Bax, and Bcl-2 protein levels were tested by western blot. Cell apoptosis was assessed through acridine orange and propidium iodide (AO/PI) staining assay and flow cytometry assay. Ruscogenin ameliorated the SFR and submandibular gland inflammation of NOD/ShiLtJ mice. Ruscogenin promoted the preservation of acinar cells and suppressed inflammation-related factors (P2X7R, NLRP3, caspase 1, and IL-1β) in submandibular gland tissues of NOD/ShiLtJ mice. Ruscogenin inhibited acinar cell apoptosis in NOD/ShiLtJ mice and reversed TNF-α-induced apoptosis and inflammation of acinar cells. NLRP3 overexpression reversed the repressive effect of Ruscogenin on TNF-α-induced inflammation and apoptosis of acinar cells. Ruscogenin ameliorated SS by inhibiting NLRP3 inflammasome activation.
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Ok SM, Ho D, Lynd T, Ahn YW, Ju HM, Jeong SH, Cheon K. Candida Infection Associated with Salivary Gland-A Narrative Review. J Clin Med 2020; 10:E97. [PMID: 33396602 PMCID: PMC7795466 DOI: 10.3390/jcm10010097] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 12/21/2020] [Accepted: 12/26/2020] [Indexed: 11/22/2022] Open
Abstract
Candida species are common global opportunistic pathogens that could repeatedly and chronically cause oral mucosa infection and create an inflammatory environment, leading to organ dysfunction. Oral Candida infections may cause temporary or permanent damage to salivary glands, resulting in the destruction of acinar cells and the formation of scar tissue. Restricted function of the salivary glands leads to discomfort and diseases of the oral mucosa, such as dry mouth and associated infection. This narrative review attempts to summarize the anatomy and function of salivary glands, the associations between Candida and saliva, the effects of Candida infection on salivary glands, and the treatment strategies. Overall, clinicians should proactively manage Candida infections by educating patients on oral hygiene management for vulnerable populations, conducting frequent checks for a timely diagnosis, and providing an effective treatment plan.
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Affiliation(s)
- Soo-Min Ok
- Department of Oral Medicine, Dental and Life Science Institute, Pusan National University, Yangsan 50612, Korea; (S.-m.O.); (Y.-W.A.); (H.-M.J.); (S.-H.J.)
- Dental Research Institute, Pusan National University Dental Hospital, Yangsan 50612, Korea
- Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (D.H.); (T.L.)
| | - Donald Ho
- Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (D.H.); (T.L.)
| | - Tyler Lynd
- Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (D.H.); (T.L.)
| | - Yong-Woo Ahn
- Department of Oral Medicine, Dental and Life Science Institute, Pusan National University, Yangsan 50612, Korea; (S.-m.O.); (Y.-W.A.); (H.-M.J.); (S.-H.J.)
- Dental Research Institute, Pusan National University Dental Hospital, Yangsan 50612, Korea
| | - Hye-Min Ju
- Department of Oral Medicine, Dental and Life Science Institute, Pusan National University, Yangsan 50612, Korea; (S.-m.O.); (Y.-W.A.); (H.-M.J.); (S.-H.J.)
- Dental Research Institute, Pusan National University Dental Hospital, Yangsan 50612, Korea
| | - Sung-Hee Jeong
- Department of Oral Medicine, Dental and Life Science Institute, Pusan National University, Yangsan 50612, Korea; (S.-m.O.); (Y.-W.A.); (H.-M.J.); (S.-H.J.)
- Dental Research Institute, Pusan National University Dental Hospital, Yangsan 50612, Korea
| | - Kyounga Cheon
- Department of Pediatric Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA; (D.H.); (T.L.)
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7
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Lin YH, Wang YC, Wu MS, Lu KC, Lin HY, Kuo HS, Chang GD, Lin CM, Hsiao C. The study of isotopic enrichment of water in human plasma and erythrocyte. FASEB J 2020; 34:13049-13062. [PMID: 32779304 DOI: 10.1096/fj.202000388rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 07/21/2020] [Accepted: 07/23/2020] [Indexed: 11/11/2022]
Abstract
Life does not sustain without water. For water, there is a natural abundance of stable isotope hydrogen and oxygen. Water molecules get across cell membranes through a plasma membrane protein, named aquaporin. Moreover, the kidney is the main organ to maintain water homeostasis. Here, we study the stable isotopic ratios of hydrogen and oxygen in human blood plasma and erythrocyte corresponding to kidney functions. We extract waters from human plasma and erythrocyte, collected from 110 participants, including 51 clinically stable outpatients with end-stage renal disease (ESRD) and 59 subjects with normal renal function (NRF). We observed that (i) both extracellular (blood plasma) and intracellular (erythrocyte) biology waters are isotopic differences between the ESRD and NRF participants, (ii) the natural abundance of isotopic waters of ESRD is hypo-isotopic, and (iii) the isotopic enrichment of water between erythrocyte and blood plasma are distinct. In addition, we introduce an empirical formula using entropy transformation to describe isotopic water enrichment for biology. Accordingly, the natural abundance of stable isotope water of blood plasma and erythrocyte may be possibly put in practice a new sign for assessments of kidney dysfunctions.
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Affiliation(s)
- Yuan-Hau Lin
- College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ying-Chi Wang
- Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.,Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
| | - Mai-Szu Wu
- College of Medicine, Taipei Medical University, Taipei, Taiwan.,Division of Nephrology, Taipei Medical University - Shuang Ho Hospital, New Taipei City, Taiwan
| | - Kuo-Cheng Lu
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Hsin-Yi Lin
- Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.,Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
| | - Hsien-Shou Kuo
- College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Geen-Dong Chang
- Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan
| | - Chun-Mao Lin
- College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chiaolong Hsiao
- Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan.,Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan
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8
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D’Agostino C, Elkashty OA, Chivasso C, Perret J, Tran SD, Delporte C. Insight into Salivary Gland Aquaporins. Cells 2020; 9:cells9061547. [PMID: 32630469 PMCID: PMC7349754 DOI: 10.3390/cells9061547] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 06/23/2020] [Accepted: 06/23/2020] [Indexed: 12/18/2022] Open
Abstract
The main role of salivary glands (SG) is the production and secretion of saliva, in which aquaporins (AQPs) play a key role by ensuring water flow. The AQPs are transmembrane channel proteins permeable to water to allow water transport across cell membranes according to osmotic gradient. This review gives an insight into SG AQPs. Indeed, it gives a summary of the expression and localization of AQPs in adult human, rat and mouse SG, as well as of their physiological role in SG function. Furthermore, the review provides a comprehensive view of the involvement of AQPs in pathological conditions affecting SG, including Sjögren's syndrome, diabetes, agedness, head and neck cancer radiotherapy and SG cancer. These conditions are characterized by salivary hypofunction resulting in xerostomia. A specific focus is given on current and future therapeutic strategies aiming at AQPs to treat xerostomia. A deeper understanding of the AQPs involvement in molecular mechanisms of saliva secretion and diseases offered new avenues for therapeutic approaches, including drugs, gene therapy and tissue engineering. As such, AQP5 represents a potential therapeutic target in different strategies for the treatment of xerostomia.
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Affiliation(s)
- Claudia D’Agostino
- Laboratory of Pathophysiological and Nutritional Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Blg G/E CP 611, B-1070 Brussels, Belgium; (C.D.); (C.C.); (J.P.)
| | - Osama A. Elkashty
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, Montreal, QC H3A 0C7, Canada; (O.A.E.); (S.D.T.)
- Oral Pathology Department, Faculty of Dentistry, Mansoura University, 35516 Mansoura, Egypt
| | - Clara Chivasso
- Laboratory of Pathophysiological and Nutritional Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Blg G/E CP 611, B-1070 Brussels, Belgium; (C.D.); (C.C.); (J.P.)
| | - Jason Perret
- Laboratory of Pathophysiological and Nutritional Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Blg G/E CP 611, B-1070 Brussels, Belgium; (C.D.); (C.C.); (J.P.)
| | - Simon D. Tran
- McGill Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, Montreal, QC H3A 0C7, Canada; (O.A.E.); (S.D.T.)
| | - Christine Delporte
- Laboratory of Pathophysiological and Nutritional Biochemistry, Faculty of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, Blg G/E CP 611, B-1070 Brussels, Belgium; (C.D.); (C.C.); (J.P.)
- Correspondence: ; Tel.: +32-2-5556210
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9
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Wang D, Zhou M, Wang Y, Sun S. Suppression of high-mobility group box 1 ameliorates xerostomia in a Sjögren syndrome-triggered mouse model. Can J Physiol Pharmacol 2020; 98:351-356. [PMID: 31935120 DOI: 10.1139/cjpp-2019-0337] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Xerostomia is a self-conscious symptom. High-mobility group box 1 (HMGB1) promotes pro-inflammatory effects in many diseases. This study aimed to clarify the role of HMGB1 in Sjögren syndrome (SS)-triggered xerostomia. Nonobese diabetic (NOD)/Ltj mice were used to establish an SS-triggered xerostomia model. The results showed that saliva production was decreased and anti-Sjögren syndrome B (anti-SSB) level was increased in SS. PCR, Western blot, and immunohistochemistry experiments indicated that the HMGB1 and aquaporin 5 (AQP5) levels were enhanced and diminished in SS compared with those in the control, respectively. While the mice were treated with anti-HMGB1, xerostomia was reversed due to the elevated saliva production and reduced anti-SSB level. In addition, it was found that the inhibition of HMGB1 restrained the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) axis activation. The TLR4 and p-IκB levels were alleviated, while the IκBα and NF-κB p65 levels were augmented. The NF-κB p65 binding activity was attenuated via the electrophoretic mobility shift assay (EMSA) after anti-HMGB1 treatment. Moreover, the repression of HMGB1 facilitated the expression of AQP5. These findings demonstrate that suppression of HMGB1 ameliorates SS-triggered xerostomia via suppressing the HMGB1/TLR4/NF-κB signaling pathway and upregulating AQP5 expression.
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Affiliation(s)
- Di Wang
- Department of Nephrology, Xijing Hospital, The First Affiliated Hospital of Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China
- Department of Nephrology, Xijing Hospital, The First Affiliated Hospital of Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China
| | - Meilan Zhou
- Department of Nephrology, Xijing Hospital, The First Affiliated Hospital of Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China
- Department of Nephrology, Xijing Hospital, The First Affiliated Hospital of Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China
| | - Yan Wang
- Department of Nephrology, Xijing Hospital, The First Affiliated Hospital of Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China
- Department of Nephrology, Xijing Hospital, The First Affiliated Hospital of Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China
| | - Shiren Sun
- Department of Nephrology, Xijing Hospital, The First Affiliated Hospital of Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China
- Department of Nephrology, Xijing Hospital, The First Affiliated Hospital of Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China
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10
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De Santis S, Serino G, Fiorentino MR, Galleggiante V, Gena P, Verna G, Liso M, Massaro M, Lan J, Troisi J, Cataldo I, Bertamino A, Pinto A, Campiglia P, Santino A, Giannelli G, Fasano A, Calamita G, Chieppa M. Aquaporin 9 Contributes to the Maturation Process and Inflammatory Cytokine Secretion of Murine Dendritic Cells. Front Immunol 2018; 9:2355. [PMID: 30386332 PMCID: PMC6198254 DOI: 10.3389/fimmu.2018.02355] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 09/24/2018] [Indexed: 01/22/2023] Open
Abstract
Dendritic cells (DCs) are the most potent antigen-presenting cells able to trigger the adaptive immune response to specific antigens. When non-self-antigens are captured, DCs switch from an “immature” to a “mature” state to fulfill their function. Among the several surface proteins involved in DCs maturation, the role of aquaporins (AQPs) is still poorly understood. Here we investigated the expression profile of Aqps in murine bone marrow derived dendritic cells (BMDCs). Among the Aqps analyzed, Aqp9 was the most expressed by DCs. Its expression level was significantly upregulated 6 h following LPS exposure. Chemical inhibition of Aqp9 led to a decreased inflammatory cytokines secretion. BMDCs from AQP9-KO mice release lower amount of inflammatory cytokines and chemokines and increased release of IL-10. Despite the reduced release of inflammatory cytokines, Aqp9-KO mice were not protected from DSS induced colitis. All together, our data indicate that AQP9 blockade can be an efficient strategy to reduce DCs inflammatory response but it is not sufficient to protect from acute inflammatory insults such as DSS induced colitis.
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Affiliation(s)
- Stefania De Santis
- National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy.,Department of Pharmacy, University of Salerno, Fisciano, Italy.,Pineta Grande Hospital, Castelvolturno, Italy
| | - Grazia Serino
- National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Maria R Fiorentino
- Harvard Medical School Division of Pediatric Gastroenterology and Nutrition and Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA, United States
| | - Vanessa Galleggiante
- National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Patrizia Gena
- Department of Medicine and Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Salerno, Italy
| | - Giulio Verna
- National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Marina Liso
- National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Monica Massaro
- National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Jinggang Lan
- Harvard Medical School Division of Pediatric Gastroenterology and Nutrition and Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA, United States
| | - Jacopo Troisi
- Department of Medicine and Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Salerno, Italy.,Theoreo srl-Spin-off Company of the University of Salerno, Salerno, Italy
| | - Ilaria Cataldo
- Department of Medicine and Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Salerno, Italy
| | | | - Aldo Pinto
- Department of Pharmacy, University of Salerno, Fisciano, Italy
| | - Pietro Campiglia
- Department of Pharmacy, University of Salerno, Fisciano, Italy.,European Biomedical Research Institute of Salerno, Salerno, Italy
| | - Angelo Santino
- Institute of Sciences of Food Production C.N.R., Unit of Lecce, Lecce, Italy
| | - Gianluigi Giannelli
- National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy
| | - Alessio Fasano
- Harvard Medical School Division of Pediatric Gastroenterology and Nutrition and Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA, United States.,European Biomedical Research Institute of Salerno, Salerno, Italy
| | - Giuseppe Calamita
- Department of Medicine and Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Salerno, Italy
| | - Marcello Chieppa
- National Institute of Gastroenterology "S. de Bellis", Research Hospital, Castellana Grotte, Italy.,Department of Pharmacy, University of Salerno, Fisciano, Italy
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11
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Effect of methotrexate combined with Sanhuang Yilong decoction on serum and synovial fluid aquaporin levels in rheumatoid arthritis dampness-heat blockage syndrome. J TRADIT CHIN MED 2018. [DOI: 10.1016/s0254-6272(18)30895-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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12
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Ichiyama T, Nakatani E, Tatsumi K, Hideshima K, Urano T, Nariai Y, Sekine J. Expression of aquaporin 3 and 5 as a potential marker for distinguishing dry mouth from Sjögren’s syndrome. J Oral Sci 2018; 60:212-220. [DOI: 10.2334/josnusd.17-0150] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Affiliation(s)
- Tomoko Ichiyama
- Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
- Department of Oral and Maxillofacial Surgery, Masuda Red Cross Hospital
| | - Eiji Nakatani
- Translational Research Informatics Center, Foundation for Biomedical Research and Innovation
| | - Kasumi Tatsumi
- Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
| | - Katsumi Hideshima
- Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
| | - Takeshi Urano
- Department of Biochemistry, Shimane University Faculty of Medicine
| | - Yoshiki Nariai
- Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
- Department of Oral and Maxillofacial Surgery, Matsue City Hospital
| | - Joji Sekine
- Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine
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13
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Aquaporins in Respiratory System. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 969:115-122. [PMID: 28258569 DOI: 10.1007/978-94-024-1057-0_7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Aquaporins (AQPs ) are water channel proteins supposed to facilitating fluid transport in alveolar space, airway humidification, pleural fluid absorption, and submucosal gland secretion . In this chapter, we mainly focus on the expression of 4 AQPs in the lungs which include AQP1, AQP2 , AQP4 and AQP5 in normal and disease status, and the experience of AQPs function from various model and transgenic mice were summarized in detail to improve our understanding of the role of AQPs in fluid balance of respiratory system. It has been suggested that AQPs play important roles in various physiology and pathophysiology conditions of different lung diseases. There still remains unclear the exact role of AQPs in lung diseases, and thus continuous efforts on elucidating the roles of AQPs in lung physiological and pathophysilogical processes are warranted.
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Kuraji M, Matsuno T, Satoh T. Astaxanthin affects oxidative stress and hyposalivation in aging mice. J Clin Biochem Nutr 2016; 59:79-85. [PMID: 27698533 PMCID: PMC5018570 DOI: 10.3164/jcbn.15-150] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Accepted: 01/08/2016] [Indexed: 11/22/2022] Open
Abstract
Oral dryness, a serious problem for the aging Japanese society, is induced by aging-related hyposalivation and causes dysphagia, dysgeusia, inadaptation of dentures, and growth of oral Candida albicans. Oxidative stress clearly plays a role in decreasing saliva secretion and treatment with antioxidants such astaxanthin supplements may be beneficial. Therefore, we evaluated the effects of astaxanthin on the oral saliva secretory function of aging mice. The saliva flow increased in astaxanthin-treated mice 72 weeks after administration while that of the control decreased by half. The plasma d-ROMs values of the control but not astaxanthin-treated group measured before and 72 weeks after treatment increased. The diacron-reactive oxygen metabolites (d-ROMs) value of astaxanthin-treated mice 72 weeks after treatment was significantly lower than that of the control group was. The plasma biological antioxidative potential (BAP) values of the control but not astaxanthin-treated mice before and 72 weeks after treatment decreased. Moreover, the BAP value of the astaxanthin-treated group 72 weeks after treatment was significantly higher than that of the control was. Furthermore, the submandibular glands of astaxanthin-treated mice had fewer inflammatory cells than the control did. Specifically, immunofluorescence revealed a significantly large aquaporin-5 positive cells in astaxanthin-treated mice. Our results suggest that astaxanthin treatment may prevent age-related decreased saliva secretion.
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Affiliation(s)
- Manatsu Kuraji
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Tokyo, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan
| | - Tomonori Matsuno
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Tokyo, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan
| | - Tazuko Satoh
- Department of Oral and Maxillofacial Surgery, School of Life Dentistry at Tokyo, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan
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Chen TY, Tang XG. Compensation of aquaporin 3 in rats after resection of two-thirds of the colon: Effect of Pulsatilla decoction. Shijie Huaren Xiaohua Zazhi 2015; 23:4871-4875. [DOI: 10.11569/wcjd.v23.i30.4871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To detect the expression of aquaporin 3 (AQP3) in rats after resection of two-thirds of the colon, and to assess the effect of Pulsatilla decoction on AQP3 expression.
METHODS: Resection of two-thirds of the colon was performed in rats. Rats were randomly divided into a normal control group, a model group, and a Chinese intervention group, with nine rats in each group. The Chinese intervention group was treated with Pulsatilla decoction. The expression of AQP3 protein and mRNA was detected by immunohistochemistry and real-time PCR, respectively.
RESULTS: At the first week, AQP3 compensation was observed in the colon of rats in the model group colon, and diarrhea was improved. At the second and fourth weeks, Pulsatilla decoction treatment significantly reduced the compensation time compared with rats in the model group, but did not alter the expression level of AQP3.
CONCLUSION: The expression of AQP3 is increased in rats after resection of two-thirds of the colon, and Pulsatilla decoction plays a positive role in promoting Aquaporin 3 compensation.
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Sato M, Kuroda S, Mansjur KQ, Khaliunaa G, Nagata K, Horiuchi S, Inubushi T, Yamamura Y, Azuma M, Tanaka E. Low-intensity pulsed ultrasound rescues insufficient salivary secretion in autoimmune sialadenitis. Arthritis Res Ther 2015; 17:278. [PMID: 26445930 PMCID: PMC4596462 DOI: 10.1186/s13075-015-0798-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Accepted: 09/24/2015] [Indexed: 11/17/2022] Open
Abstract
Introduction Low-intensity pulsed ultrasound (LIPUS) has been known to promote bone healing by nonthermal effects. In recent studies, LIPUS has been shown to reduce inflammation in injured soft tissues. Xerostomia is one of the most common symptoms in Sjögren syndrome (SS). It is caused by a decrease in the quantity or quality of saliva. The successful treatment of xerostomia is still difficult to achieve and often unsatisfactory. The aim of this study is to clarify the therapeutic effects of LIPUS on xerostomia in SS. Methods Human salivary gland acinar (NS-SV-AC) and ductal (NS-SV-DC) cells were cultured with or without tumor necrosis factor-α (TNF-α; 10 ng/ml) before LIPUS or sham exposure. The pulsed ultrasound signal was transmitted at a frequency of 1.5 MHz or 3 MHz with a spatial average intensity of 30 mW/cm2 and a pulse rate of 20 %. Cell number, net fluid secretion rate, and expression of aquaporin 5 (AQP5) and TNF-α were subsequently analyzed. Inhibitory effects of LIPUS on the nuclear factor κB (NF-κB) pathway were determined by Western blot analysis. The effectiveness of LIPUS in recovering salivary secretion was also examined in a MRL/MpJ/lpr/lpr (MRL/lpr) mouse model of SS with autoimmune sialadenitis. Results TNF-α stimulation of NS-SV-AC and NS-SV-DC cells resulted in a significant decrease in cell number and net fluid secretion rate (p < 0.01), whereas LIPUS treatment abolished them (p < 0.05). The expression changes of AQP5 and TNF-α were also inhibited in LIPUS treatment by blocking the NF-κB pathway. Furthermore, we found that mRNA expression of A20, a negative feedback regulator, was significantly increased by LIPUS treatment after TNF-α or interleukin 1β stimulation (NS-SV-AC, p < 0.01; NS-SV-DC, p < 0.05). In vivo LIPUS exposure to MRL/lpr mice exhibited a significant increase in both salivary flow and AQP5 expression by reducing inflammation in salivary glands (p < 0.01). Conclusions These results suggest that LIPUS upregulates expression of AQP5 and inhibits TNF-α production. Thus, LIPUS may restore secretion by inflamed salivary glands. It may synergistically activate negative feedback of NF-κB signaling in response to inflammatory stimulation. Collectively, LIPUS might be a new strategic therapy for xerostomia in autoimmune sialadenitis with SS. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0798-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Minami Sato
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
| | - Shingo Kuroda
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
| | - Karima Qurnia Mansjur
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
| | - Ganzorig Khaliunaa
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
| | - Kumiko Nagata
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
| | - Shinya Horiuchi
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
| | - Toshihiro Inubushi
- Genetic Disease Program, Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
| | - Yoshiko Yamamura
- Department of Oral Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
| | - Masayuki Azuma
- Department of Oral Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
| | - Eiji Tanaka
- Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. .,Department of Orthodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
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Wang W, Wang X, Ma L, Zhang R. Histamine downregulates aquaporin 5 in human nasal epithelial cells. Am J Rhinol Allergy 2015; 29:188-92. [PMID: 25781725 DOI: 10.2500/ajra.2015.29.4181] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Aquaporin 5 (AQP5) is a water-specific channel protein. It is thought to be a key participant in fluid secretion and a rate-limiting barrier to the secretion seen during allergic inflammation. We sought to determine the effect of histamine on AQP5 expression in human nasal epithelial cells (HNEpC). METHODS HNEpC cells were cultured with four concentrations of histamine in vitro. The phosphorylation of cyclic adenosine monophosphate-responsive element binding protein (CREB) at serine 133 and the AQP5 protein were measured by using immunocytochemistry and Western blotting. Real-time polymerase chain reaction was used to detect AQP5 messenger ribonucleic acid (mRNA). RESULTS Concentration-dependent histamine induced-inhibition of CREB phosphorylation at serine 133 in HNEpC cells was observed, and AQP5 mRNA and protein were also downregulated in a concentration-dependent fashion. CONCLUSION Histamine downregulates AQP5 production in HNEpC cells by inhibiting CREB phosphorylation at serine 133.
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Affiliation(s)
- Weiwei Wang
- Department of Anatomy, Schools of Medicine and Nursing Sciences, Huzhou University, China
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Brune K, Frank J, Schwingshackl A, Finigan J, Sidhaye VK. Pulmonary epithelial barrier function: some new players and mechanisms. Am J Physiol Lung Cell Mol Physiol 2015; 308:L731-45. [PMID: 25637609 DOI: 10.1152/ajplung.00309.2014] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Accepted: 01/27/2015] [Indexed: 12/20/2022] Open
Abstract
The pulmonary epithelium serves as a barrier to prevent access of the inspired luminal contents to the subepithelium. In addition, the epithelium dictates the initial responses of the lung to both infectious and noninfectious stimuli. One mechanism by which the epithelium does this is by coordinating transport of diffusible molecules across the epithelial barrier, both through the cell and between cells. In this review, we will discuss a few emerging paradigms of permeability changes through altered ion transport and paracellular regulation by which the epithelium gates its response to potentially detrimental luminal stimuli. This review is a summary of talks presented during a symposium in Experimental Biology geared toward novel and less recognized methods of epithelial barrier regulation. First, we will discuss mechanisms of dynamic regulation of cell-cell contacts in the context of repetitive exposure to inhaled infectious and noninfectious insults. In the second section, we will briefly discuss mechanisms of transcellular ion homeostasis specifically focused on the role of claudins and paracellular ion-channel regulation in chronic barrier dysfunction. In the next section, we will address transcellular ion transport and highlight the role of Trek-1 in epithelial responses to lung injury. In the final section, we will outline the role of epithelial growth receptor in barrier regulation in baseline, acute lung injury, and airway disease. We will then end with a summary of mechanisms of epithelial control as well as discuss emerging paradigms of the epithelium role in shifting between a structural element that maintains tight cell-cell adhesion to a cell that initiates and participates in immune responses.
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Affiliation(s)
- Kieran Brune
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland
| | - James Frank
- The Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco VA Medical Center, and NCIRE/Veterans Health Research Institute, San Francisco, California
| | - Andreas Schwingshackl
- Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee
| | - James Finigan
- Division of Oncology, Cancer Center, National Jewish Health, Denver, Colorado
| | - Venkataramana K Sidhaye
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland;
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Fang F, Liu CY, Zhang J, Zhu L, Qian YX, Yi J, Xiang ZH, Wang H, Jiang H. Involvement of MAPK ERK activation in upregulation of water channel protein aquaporin 1 in a mouse model of Bell's palsy. J Mol Neurosci 2014; 56:164-76. [PMID: 25527444 DOI: 10.1007/s12031-014-0477-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Accepted: 12/10/2014] [Indexed: 01/26/2023]
Abstract
The aim of this study is to immunolocalize the aquaporin 1 water channel protein (AQP1) in Schwann cells of idiopathic facial nerve and explore its possible role during the development of facial palsy induced by herpes simplex virus type 1 (HSV-1). HSV-1 was inoculated into the surface of posterior auricle of mouse to establish a paralyzed animal model. In HSV-1-induced facial palsy mice, protein levels of AQP1 significantly increased on the 9th to 16th day after inoculation of HSV-1. The upregulation of AQP1 was closely related to the intratemporal facial nerve edema in facial nerve canal, which was also consistent with the symptom of facial palsy in mice. In a hypoxia model of Schwann cells in vitro, we found that U0126, an ERK antagonist, inhibited not only morphological changes of cultures Schwann cells but also upregulation of both AQP1 and phosphorylated ERK. Combined with increased phosphorylated ERK in HSV-1-induced facial palsy mice, we inferred that ERK MAPK pathway might also be involved in increased AQP1 in mouse model of Bell's palsy. Although the precise mechanism needs to be further explored, our findings suggest that AQP1 in Schwann cells of intratemporal facial nerve is involved in the evolution of facial palsy induced by HSV-1 and may play an important role in the pathogenesis of this disease. AQP1 might be a potential target, and the ERK antagonist U0126 could be a new drug for the treatment of HSV-1-induced Bell's palsy in an early stage.
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Affiliation(s)
- Fan Fang
- Department of Plastic Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, People's Republic of China
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Multiple intracranial metastatic tumor case report and aquaporin water channel-related research. Cell Biochem Biophys 2014; 71:1015-21. [PMID: 25342397 DOI: 10.1007/s12013-014-0303-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
This case report deals with multiple intracranial metastatic tumors and studies of expression and regulation characteristics of aquaporins (AQPs) of cerebellar metastatic tumor and brain tissue surrounding tumor. In this work, we try to understand the role of abnormal expression of AQPs in formation and elimination of brain edema and provide new ideas for the treatment of brain edema induced by tumor. The work involves resection of intracranial occupying lesions to get cerebellar metastatic tumor organization. Total RNA was extracted, RT-PCR was done, and immunohistochemical staining was done to study the expression and regulation characteristics of AQPs. We found that AQP4 had a high expression in the peritumoral brain tissue and no expression in the center of brain metastasis tumor organization. Around the tumor tissue, the AQP4 staining was junior in the more distant region from tumor and it added significantly in close to the tumor tissue region. It demonstrated that the AQP4 expression was upregulated, obviously with the distance drawing near gradually to tumor tissue. In addition, stained AQP1 was not observed on cerebellar metastatic tumor and peritumoral brain microvascular endothelial cells. The phenomenon that AQP4 had an increased expression in the surrounding region of cerebellar metastatic tumor and, moreover, increased significantly in the region next to the cerebellar metastatic tumor tightly is probably related to the formation of peritumoral brain edema and plays an important role in cytotoxic brain edema mechanism. AQP1 was not expressed on cerebellar metastatic tumor and peritumoral brain tissue microvascular endothelial cells, and this may be an important factor that the peritumoral interstitial brain edema is removed ineffectively to cause 'small tumor, big edema.'
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Temporal and spatial distribution of the aquaporin 1 in spinal cord and dorsal root ganglia after traumatic injuries of the sciatic nerve. Childs Nerv Syst 2014; 30:1679-86. [PMID: 25119150 DOI: 10.1007/s00381-014-2472-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Accepted: 06/12/2014] [Indexed: 10/24/2022]
Abstract
PURPOSE The aquaporin family comprises a large family of integral membrane proteins that enable the movement of water and other small, neutral solutes across plasma membranes. Although function and mechanism of aquaporins in central nervous system injury have been reported, the pathophysiologic role of aquaporin 1 (AQP1) in peripheral nerve has not been extensively documented. In the present study, we aimed to study the temporal and spatial distribution of AQP1 in spinal cord and dorsal root ganglia after sciatic nerve injury. METHODS Forty-eight adult female mice were randomly divided into four groups (intact controls, sham operated, cut injury, and crush injury). Animals receiving cut or crush injuries were sacrificed at the 2nd, 24th, and 48th postoperative hours. Spinal cord samples at the level of lumbosacral intumescences and corresponding dorsal root ganglia on the experimental and contralateral side were dissected free and proceeded to AQP1 immunohistochemistry. RESULTS Our quantitative estimations revealed that a sharp increase in AQP1 immunoreactivity at the 24th postoperative hour was observed. This sharp increase was no more evident at 48 h after sciatic nerve injury. Identical peak was observed after both cut and crush injuries. CONCLUSIONS We demonstrated that there was a temporal relationship with an increased expression of AQP1 following injury sustained to the sciatic nerve that was significantly observed in dorsal root ganglia and spinal cord. Those expressions were also subsided over time.
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AQP1 expression in human gingiva and its correlation with periodontal and peri-implant tissue alterations. Acta Histochem 2014; 116:898-904. [PMID: 24698289 DOI: 10.1016/j.acthis.2014.02.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 02/25/2014] [Accepted: 02/26/2014] [Indexed: 11/22/2022]
Abstract
Aquaporins (AQPs) are a family of hydrophobic integral membrane proteins that function as transmembrane channels and play an important role in tissue homeostasis. Aquaporin-1 (AQP1), in particular, has been reported to be involved in several biological processes including inflammation, angiogenesis, wound healing and others. Periodontitis and peri-implantitis can be defined as inflammatory processes that affect the tissues surrounding a tooth or an osseointegrated implant, respectively. To date, there are limited data about the involvement of AQPs in these diseases. The aim of this study was to evaluate the possible link between the histomorphological alterations and the expression of AQP1 in healthy, pathological and healed periodontal and peri-implant gingival tissues. The results obtained showed that changes in organization of collagen fibers were observed in periodontitis and peri-implantitis, together with an increase in the percentage of area occupied by inflammatory cell infiltration and an increase of AQP1 immunostaining, which was located in the endothelial cells of the vessels within the lamina propria. Moreover, in healed periodontal and peri-implant mucosa a restoration of histomorphological alterations was observed together with a concomitant decrease of AQP1 immunostaining. These data suggested a possible link between the degree of inflammatory state and the presence of AQP1, where the latter could be involved in the chain of inflammatory reactions triggered at periodontal and peri-implant levels.
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Schey KL, Wang Z, L Wenke J, Qi Y. Aquaporins in the eye: expression, function, and roles in ocular disease. Biochim Biophys Acta Gen Subj 2013; 1840:1513-23. [PMID: 24184915 DOI: 10.1016/j.bbagen.2013.10.037] [Citation(s) in RCA: 92] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 10/22/2013] [Accepted: 10/23/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND All thirteen known mammalian aquaporins have been detected in the eye. Moreover, aquaporins have been identified as playing essential roles in ocular functions ranging from maintenance of lens and corneal transparency to production of aqueous humor to maintenance of cellular homeostasis and regulation of signal transduction in the retina. SCOPE OF REVIEW This review summarizes the expression and known functions of ocular aquaporins and discusses their known and potential roles in ocular diseases. MAJOR CONCLUSIONS Aquaporins play essential roles in all ocular tissues. Remarkably, not all aquaporin function as a water permeable channel and the functions of many aquaporins in ocular tissues remain unknown. Given their vital roles in maintaining ocular function and their roles in disease, aquaporins represent potential targets for future therapeutic development. GENERAL SIGNIFICANCE Since aquaporins play key roles in ocular physiology, an understanding of these functions is important to improving ocular health and treating diseases of the eye. It is likely that future therapies for ocular diseases will rely on modulation of aquaporin expression and/or function. This article is part of a Special Issue entitled Aquaporins.
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Affiliation(s)
- Kevin L Schey
- Department of Biochemistry, Vanderbilt School of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
| | - Zhen Wang
- Department of Biochemistry, Vanderbilt School of Medicine, Vanderbilt University, Nashville, TN 37232, USA
| | - Jamie L Wenke
- Department of Biochemistry, Vanderbilt School of Medicine, Vanderbilt University, Nashville, TN 37232, USA
| | - Ying Qi
- Department of Biochemistry, Vanderbilt School of Medicine, Vanderbilt University, Nashville, TN 37232, USA
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Zhang J, Xiong Y, Lu LX, Wang H, Zhang YF, Fang F, Song YL, Jiang H. AQP1 expression alterations affect morphology and water transport in Schwann cells and hypoxia-induced up-regulation of AQP1 occurs in a HIF-1α-dependent manner. Neuroscience 2013; 252:68-79. [PMID: 23948641 DOI: 10.1016/j.neuroscience.2013.08.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2013] [Revised: 07/05/2013] [Accepted: 08/03/2013] [Indexed: 11/13/2022]
Abstract
Aquaporin-1 (AQP1) is the principle water channel in the peripheral nervous system (PNS) and is specifically localized to Schwann cells in the PNS. However, the pathophysiological role of AQP1 in peripheral nerves is poorly understood. Here, we utilized RNA interference by lentiviral transduction to specifically down-regulate AQP1 expression and a lentiviral overexpression protocol to up-regulate AQP1 expression, in primary Schwann cell cultures. AQP1 gene silencing resulted in a cell shrinkage phenotype, while AQP1 gene overexpression caused a cell swelling phenotype, as validated by cell volume determinations. Secondly, we utilized an in vitro hypoxia model in Schwann cells to mimic in vivo facial nerve injury. We demonstrated that AQP1 expression was induced within 8h following hypoxia injury in vitro, and that AQP1 knockdown (KD) caused the cells to resist edema following hypoxia. Finally, we investigated the hypoxic regulation of the AQP1 gene, as well as the involvement of Hypoxia-inducible factor-1α (HIF-1α) in AQP1 modulation and we found that KD of HIF-1α decreased hypoxia-dependent induction of endogenous AQP1 expression at both the mRNA and protein levels. Taken together, these results indicate that (1) AQP1 is an important factor responsible for the fast water transport of cultured Schwann cells and is involved in cell plasticity; (2) AQP1 alterations may be a primary factor in hypoxia-induced peripheral nerve edema; (3) HIF-1α participates in the hypoxic induction of the AQP1 gene; (4) AQP1 inhibition might provide a new therapeutic alternative for the treatment of some forms of peripheral nerve edema.
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Affiliation(s)
- J Zhang
- Department of Plastic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; Department of Plastic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China
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Altunbas K, Cevik–Demirkan A, Ozden-Akkaya O, Akosman MS. Renal expression and functions of aquaporin 1 and aquaporin 4 in cattle. Biotech Histochem 2013; 88:350-5. [DOI: 10.3109/10520295.2013.789126] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Hallstrand TS, Kippelen P, Larsson J, Bougault V, van Leeuwen JC, Driessen JMM, Brannan JD. Where to from here for exercise-induced bronchoconstriction: the unanswered questions. Immunol Allergy Clin North Am 2013; 33:423-42, ix. [PMID: 23830134 DOI: 10.1016/j.iac.2013.02.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The role of epithelial injury is an unanswered question in those with established asthma and in elite athletes who develop features of asthma and exercise-induced bronchorestriction (EIB) after years of training. The movement of water in response to changes in osmolarity is likely to be an important signal to the epithelium that may be central to the onset of EIB. It is generally accepted that the mast cell and its mediators play a major role in EIB and the presence of eosinophils is likely to enhance EIB severity.
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Affiliation(s)
- Teal S Hallstrand
- Division of Pulmonary and Critical Care, University of Washington, Department of Medicine, 1959 NE Pacific Street, Box 356166, Seattle, WA 98195-6522, USA.
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Yamamura Y, Motegi K, Kani K, Takano H, Momota Y, Aota K, Yamanoi T, Azuma M. TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation. J Cell Mol Med 2012; 16:1766-75. [PMID: 21973049 PMCID: PMC3822690 DOI: 10.1111/j.1582-4934.2011.01456.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Sjögren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-α plays an important role in the destruction of acinar structures. Here we examined TNF-α's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF-α, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-α treatment were investigated. TNF-α-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-α. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-κB activity in the TNF-α-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-α suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IκBα cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-α in NS-SV-AC cells. Therefore, our results may indicate that TNF-α inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4.
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Affiliation(s)
- Yoshiko Yamamura
- Department of Oral Medicine, Institute of Health Biosciences, The University of Tokushima Graduate Faculty of Dentistry, Tokushima, Japan
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Neocleous V, Skordis N, Shammas C, Efstathiou E, Mastroyiannopoulos NP, Phylactou LA. Identification and characterization of a novel X-linked AVPR2 mutation causing partial nephrogenic diabetes insipidus: a case report and review of the literature. Metabolism 2012; 61:922-30. [PMID: 22386940 DOI: 10.1016/j.metabol.2012.01.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2011] [Revised: 01/04/2012] [Accepted: 01/05/2012] [Indexed: 11/23/2022]
Abstract
X-linked nephrogenic diabetes insipidus (NDI) is a rare disease characterized by a malfunctioning renal response to the antidiuretic hormone arginine vasopressin (AVP) due to mutations in the AVPR2 gene. A limited number of mutations in the AVPR2 gene resulting in partial phenotype have been described so far. In this mini-review the retrospective analysis of 13 known AVPR2 mutations that have been previously shown in vitro to partially abolish AVPR2 function is described, along with a novel mutation diagnosed in a kindred with partial NDI. In the present study, a 14 year old male and his 73 year old maternal grandfather were diagnosed with partial NDI based on the clinical phenotype, the water deprivation test and the inadequate response to 1-desamino-8-d-arginine vasopressin (DDAVP) administration. Sequencing analysis of the AVPR2 gene revealed the novel missense mutation p.N317S (g.1417A > G) in both patients. This mutation was re-created by site directed mutagenesis in an AVPR2 cDNA expression vector and was functionally characterized, in terms of arginine vasopressin (AVP) and DDAVP response. AVPR2 activity of the p.N317S mutant receptor after the AVP and DDAVP administration, as assessed by cAMP production was reduced and impaired when compared to cells that expressed the wild type AVPR2 gene. In conclusion, the affected members of this family have X-linked NDI with partial resistance to AVP, due to a missense mutation in the AVPR2 gene.
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Affiliation(s)
- Vassos Neocleous
- Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, P.O. Box 23462, 1683 Nicosia, Cyprus
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Yamamura Y, Aota K, Yamanoi T, Kani K, Takano H, Momota Y, Motegi K, Azuma M. DNA demethylating agent decitabine increases AQP5 expression and restores salivary function. J Dent Res 2012; 91:612-7. [PMID: 22522773 DOI: 10.1177/0022034512446343] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Xerostomia is the symptom of oral dryness resulting most frequently, but not exclusively, from salivary gland hypofunction. Because the prevalence of xerostomia may increase with age, it has multiple oral health consequences in aging populations. In the present study, we demonstrate that the in vivo administration of 5-aza-2'-deoxycytidine (5-Aza-CdR; decitabine), a DNA demethylating agent, to the murine aging model C57BL/6CrSlc mice (24 wks old) increased the volumes of salivary flow compared with those of control mice. Western blot analysis and immunohistochemical staining demonstrated the augmented expression of AQP5 protein in the salivary glands of 5-Aza-CdR-treated mice compared with those of control mice. In addition, AQP5 protein expression levels in 5-Aza-CdR-treated old mice (27 wks old) were much higher than those in untreated and young mice (6 wks old). Global methylation levels in the salivary glands were significantly lower in the 5-Aza-CdR-treated mice than in the untreated mice. Moreover, the induction of demethylation in the AQP5 promoter of 5-Aza-CdR-treated mice was stronger than in the control mice. Analysis of our data therefore suggests that a DNA demethylating agent may be a useful drug for restoring hyposalivation in elderly individuals, thereby leading to the resolution of xerostomia.
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Affiliation(s)
- Y Yamamura
- Department of Oral Medicine, Institute of Health Biosciences, The University of Tokushima, Graduate Faculty of Dentistry, Tokushima, Japan
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Yoshii T, Harada F, Saito I, Nozawa-Inoue K, Kawano Y, Maeda T. Immunoexpression of aquaporin-1 in the rat periodontal ligament during experimental tooth movement. Biomed Res 2012; 33:225-33. [DOI: 10.2220/biomedres.33.225] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Barbara B. Aquaporin biology and nervous system. Curr Neuropharmacol 2010; 8:97-104. [PMID: 21119880 PMCID: PMC2923373 DOI: 10.2174/157015910791233204] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2009] [Revised: 03/01/2010] [Accepted: 04/07/2010] [Indexed: 12/21/2022] Open
Abstract
Our understanding of the movement of water through cell membranes has been greatly advanced by the discovery of a family of water-specific, membrane-channel proteins: the Aquaporins (AQPs). These proteins are present in organisms at all levels of life, and their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis.Phenotype analysis of AQP knock-out mice has confirmed the predicted role of AQPs in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Regarding their expression in nervous system, there are evidences suggesting that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in cerebrospinal fluid formation, neuronal signal transduction and information processing.Moreover, a number of recent studies have revealed the importance of mammalian AQPs in both physiological and pathophysiological mechanisms and have suggested that pharmacological modulation of AQP expression and activity may provide new tools for the treatment of variety of human disorders in which water and small solute transport may be involved. For all the AQPs, new contributions to physiological functions are likely to be discovered with ongoing work in this rapidly expanding field of research.
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Affiliation(s)
- Buffoli Barbara
- Division of Human Anatomy, Department of Biomedical Sciences and Biotechnologies, University of Brescia, V.le Europa 11, 25123 Brescia, Italy
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Wang W, Zheng M. Nuclear factor kappa B pathway down-regulates aquaporin 5 in the nasal mucosa of rats with allergic rhinitis. Eur Arch Otorhinolaryngol 2010; 268:73-81. [PMID: 20490816 DOI: 10.1007/s00405-010-1282-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2009] [Accepted: 05/06/2010] [Indexed: 12/19/2022]
Abstract
Nuclear factor kappa B (NF-κB) induces gene transcription by binding CREB-binding protein (CBP). The aim of the study was to detect the mechanisms by which NF-κB pathway regulated aquaporin 5 (AQP5) in the nasal mucosa of rats with allergic rhinitis (AR). Rats were divided into control (group C), model (group M), low-dose proline dithiocarbamate (PDTC) (group L) and high-dose PDTC (group H) groups. AR model was established by the sensitization with ovalbumin, then groups L and H were treated with PDTC (50 or 100 mg/kg/day) for 5 days. AQP5, interleukin-1β, NF-κBp65 and phosphorylated cAMP-response element binding protein (p-CREB) were detected by immunohistochemistry, Western blotting or real-time PCR. AQP5 expression in group M was lower than in group C, but in groups L and H it increased. NF-κBp65 expression in group M was higher than group C, but in groups L and H it reduced. p-CREB expression in group M was lower than group C, but in groups L and H it increased. Interleukin-1β gene level in group M was higher than group C, but in groups L and H it was lower. These data show that the NF-κB pathway could down-regulate AQP5 by interleukin-1β which inhibited CREB phosphorylation or by NF-κBp65 which competitively bound CBP.
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Affiliation(s)
- Weiwei Wang
- Fujian Medical University, No. 88, Jiaotong Road, Fuzhou, 350004, Fujian, China
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Laforenza U, Gastaldi G, Polimeni M, Tritto S, Tosco M, Ventura U, Scaffino MF, Yasui M. Aquaporin-6 is expressed along the rat gastrointestinal tract and upregulated by feeding in the small intestine. BMC PHYSIOLOGY 2009; 9:18. [PMID: 19811639 PMCID: PMC2765416 DOI: 10.1186/1472-6793-9-18] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/18/2009] [Accepted: 10/07/2009] [Indexed: 11/30/2022]
Abstract
Background Several aquaporins (a family of integral membrane proteins) have been recently identified in the mammalian gastrointestinal tract, and their involvement in the movement of fluid and small solutes has been suggested. In this direction we investigated, in some regions of the rat gastrointestinal tract, the presence and localization of aquaporin-6, given its peculiar function as an ion selective channel. Results RT-PCR and immunoblotting experiments showed that aquaporin-6 was expressed in all the investigated portions of the rat gastrointestinal tract. The RT-PCR experiments showed that aquaporin-6 transcript was highly expressed in small intestine and rectum, and less in stomach, caecum and colon. In addition, jejunal mRNA expression was specifically stimulated by feeding. Immunoblotting analysis showed a major band with a molecular weight of about 55 kDa corresponding to the aquaporin-6 protein dimer; this band was stronger in the stomach and large intestine than in the small intestine. Immunoblotting analysis of brush border membrane vesicle preparations showed an intense signal for aquaporin-6 protein. The results of in situ hybridization experiments demonstrate that aquaporin-6 transcript is present in the isthmus, neck and basal regions of the stomach lining, and throughout the crypt-villus axis in both small and large intestine. In the latter regions, immunohistochemistry revealed strong aquaporin-6 labelling in the apical membrane of the surface epithelial cells, while weak or no labelling was observed in the crypt cells. In the stomach, an intense staining was observed in mucous neck cells and lower signal in principal cells and some parietal cells. Conclusion The results indicate that aquaporin-6 is distributed throughout the gastrointestinal tract. Aquaporin-6 localization at the apical pole of the superficial epithelial cells and its upregulation by feeding suggest that it may be involved in movements of water and anions through the epithelium of the villi.
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Affiliation(s)
- Umberto Laforenza
- Department of Physiology, Section of Human Physiology, University of Pavia, Via Forlanini 6, 27100, Pavia, Italy.
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Sasaki Y, Tsubota K, Kawedia JD, Menon AG, Yasui M. The difference of aquaporin 5 distribution in acinar and ductal cells in lacrimal and parotid glands. Curr Eye Res 2008; 32:923-9. [PMID: 18027168 DOI: 10.1080/02713680701733076] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
PURPOSE This study was designed to clarify the physiological function and tissue distribution of aquaporin 5 (AQP5) in the lacrimal and parotid glands. METHODS Saliva and tear volumes were compared in AQP5 knockout (AQP5-/-) mice and wild-type mice. Immunohistochemistry and immunoblot analysis were performed in wild-type and AQP5-/- mice. RESULTS Immunofluorescence of AQP5 staining showed that AQP5 was localized mainly in the ductal cells rather than in the acinar cells of the lacrimal gland. In contrast, in the parotid gland, AQP5 was observed abundantly in acinar cells with undetectable staining in ductal cells. Tear secretion was not changed in AQP5-/- mouse, although saliva secretion was significantly reduced. CONCLUSIONS AQP5 distribution in acinar cells and ductal cells was completely opposite in the lacrimal and parotid glands. The physiological role of AQP5 might be dependent on the characteristic tissue distribution of the protein in the lacrimal and parotid glands.
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Affiliation(s)
- Yasumasa Sasaki
- Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
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Kim MY, Kim YK, Jung YW, Kim WT, Kwon TH, Lee DS. The Protective Effect of Simvastatin on Monocrotaline-Induced Pulmonary Hypertension in Rats. Korean Circ J 2008. [DOI: 10.4070/kcj.2008.38.6.313] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- Mi Young Kim
- Department of Pediatrics, Dongguk University College of Medicine, Gyeongju, Korea
| | - Young Kyu Kim
- Department of Physiology, Dongguk University College of Medicine, Gyeongju, Korea
| | - Yong Wook Jung
- Department of Anatomy, Dongguk University College of Medicine, Gyeongju, Korea
| | - Woo Taek Kim
- Department of Pediatrics, Daegu Catholic University College of Medicine, Daegu, Korea
| | - Tae Hwan Kwon
- Department of Physiology, Kyungpook National University College of Medicine, Daegu, Korea
| | - Dong Seok Lee
- Department of Pediatrics, Dongguk University College of Medicine, Gyeongju, Korea
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Nandasena BGTL, Suzuki A, Aita M, Kawano Y, Nozawa-Inoue K, Maeda T. Immunolocalization of aquaporin-1 in the mechanoreceptive Ruffini endings in the periodontal ligament. Brain Res 2007; 1157:32-40. [PMID: 17553469 DOI: 10.1016/j.brainres.2007.04.033] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2007] [Revised: 04/11/2007] [Accepted: 04/11/2007] [Indexed: 10/23/2022]
Abstract
Previous ultrastructural studies have suggested an axon-Schwann cell interaction in the periodontal Ruffini ending, a primary mechanoreceptor. However, no information is available on the transport mechanism between them. The present study examined the immunolocalization of aquaporin-1 (AQP1) and -4 (AQP4), a member of the water-selective channel, in the periodontal Ruffini endings of the rat incisors and trigeminal ganglion. In addition, the expression of mRNA for AQP1 and 4 was detected in the trigeminal ganglion by a RT-PCR technique. A single PCR product of the sizes anticipated for AQP1 and 4 was detectable in a reverse transcripted cDNA sample from the trigeminal ganglion, whose neurons innervate the periodontal Ruffini endings. An AQP1 immunoreaction was recognizable in the axon terminals of the periodontal Ruffini endings as well as their associated terminal Schwann cells, as confirmed with a double staining with AQP1 and either PGP9.5 or S-100 protein. However, no immunoreaction for AQP4 was found in periodontal Ruffini endings. Although the AQP4 immunoreaction was localized in some satellite cells - but never in neurons - of the trigeminal ganglion, 16.1% trigeminal neurons showed the AQP1 immunoreaction. Furthermore, the AQP1 immunoreaction was found in certain satellite cells which surrounded AQP1-positive or -negative neurons. An analysis of a cross-sectional area of these positive neurons demonstrated that approximately 66.9% of the positive neurons were 400-1000 microm2 (671.4+/-172.4 microm2), indicating that they could be categorized as medium-sized neurons which mediate mechanotransduction. These findings suggest that AQP1 controls water transport in the periodontal Ruffini endings.
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Lee HJ, Lee YJ, Kwon HC, Bae S, Kim SH, Min JJ, Cho CK, Lee YS. Radioprotective effect of heat shock protein 25 on submandibular glands of rats. THE AMERICAN JOURNAL OF PATHOLOGY 2006; 169:1601-11. [PMID: 17071584 PMCID: PMC1780208 DOI: 10.2353/ajpath.2006.060327] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Irradiation (IR) is a fundamental treatment modality for head and neck malignancies. However, a significant drawback of IR treatment is irreversible damage of salivary gland in the IR field. In the present study, we investigated whether heat shock protein (HSP) 25 could be used as a radioprotective molecule for radiation-induced salivary gland damage in rats. HSP25 as well as inducible HSP70 (HSP70i) that were delivered to the salivary gland via an adenoviral vector significantly ameliorated radiation-induced salivary fluid loss. Radiation-induced apoptosis, caspase-3 activation, and poly(ADP-ribose) polymerase cleavage in acinar cells, granular convoluted cells, and intercalated ductal cells were also inhibited by HSP25 or HSP70i transfer. The alteration of salivary contents, including amylase, protein, Ca+, Cl-, and Na+, was also attenuated by HSP25 transfer. Histological analysis revealed almost no radiation-induced damage in salivary gland when HSP25 was transferred. Aquaporin 5 expression in salivary gland was inhibited by radiation; and HSP25 transfer to salivary gland prevented this alteration. The protective effect of HSP70i on radiation-induced salivary gland damage was less or delayed than that of HSP25. These results indicate that HSP25 is a good candidate molecule to protect salivary gland from the toxicity of IR.
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Affiliation(s)
- Hae-June Lee
- Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-Dong, Nowon-Ku, Seoul 139-706, Korea
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Nomura J, Horie I, Seto M, Nagai K, Hisatsune A, Miyata T, Isohama Y. All-trans retinoic acid increases expression of aquaporin-5 and plasma membrane water permeability via transactivation of Sp1 in mouse lung epithelial cells. Biochem Biophys Res Commun 2006; 351:1048-53. [PMID: 17097063 DOI: 10.1016/j.bbrc.2006.10.159] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2006] [Accepted: 10/28/2006] [Indexed: 11/25/2022]
Abstract
Aquaporin-5 (AQP5) is a water-selective channel protein that is expressed in lacrimal glands, salivary glands, and distal lung. Several studies using AQP5 knockout mice have revealed that AQP5 plays an important role in maintaining water homeostasis in the lung. We report here that all-trans retinoic acid (atRA) increases plasma membrane water permeability, AQP5 mRNA and protein expression, and AQP5 promoter activity in MLE-12 cells. The promoter activation induced by atRA was diminished by mutation at the Sp1/Sp3 binding element (SBE), suggesting that the SBE mediates the effects of atRA. In addition, atRA increased the binding of Sp1 to the SBE without changing the levels of Sp1 in the nucleus. Taken together, our data indicate that atRA increases AQP5 expression through transactivation of Sp1, leading to an increase in plasma membrane water permeability.
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Affiliation(s)
- Johji Nomura
- Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
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Affiliation(s)
- Fred G Silva
- The United States and Canadian Academy of Pathology, Emory University and the Medical college of Georgia, Augusta, GA 30909, USA.
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Jin SY, Liu YL, Xu LN, Jiang Y, Wang Y, Yang BX, Yang H, Ma TH. Cloning and characterization of porcine aquaporin 1 water channel expressed extensively in gastrointestinal system. World J Gastroenterol 2006; 12:1092-7. [PMID: 16534851 PMCID: PMC4087902 DOI: 10.3748/wjg.v12.i7.1092] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To clone and characterize the porcine aquaporins (AQPs) in the gastrointestinal system.
METHODS: A PCR-based cloning strategy and RACE were used to clone full-length AQP coding sequence from reversely transcribed pig liver cDNA. Stopped-flow light scattering and a YFP-based fluorescence method were used to measure the osmotic water permeability of erythrocytes and the stably transfected CHO cells. RT-PCR, Northern blot, and immunohistochemistry were used to determine the gastrointestinal expression and localization of cloned AQPs. Protein expression in transfected cells and red blood cells was analyzed by Western blot.
RESULTS: An 813 bp cDNA encoding a 271 amino acid porcine aquaporin (designated pAQP1) was cloned from liver mRNA (pAQP1 has a 93% identity with human AQP1 and contains two NPA motifs conserved in AQP family, one consensus sequence for N-linked glycosylation, and one mercury-sensitive site at cysteine 191). RT-PCR analysis revealed extensive expression of pAQP1 mRNA in porcine digestive glands and gut. Northern blot showed a single 3.0 kb transcript in selected digestive organs. pAQP1 protein was localized at central lacteals of the small intestine, microvessles of salivary glands, as well as epithelium of intrahepatic bile ducts by immunoperoxydase. High osmotic water permeability that is inhibitable by HgCl2 was detected in porcine erythrocytes and CHO cells stably transfected with pAQP1 cDNA. Immunoblot analysis of porcine erythrocytes and pAQP-transfected CHO cells revealed an unglycosylated 28 ku band and larger glycosylated proteins.
CONCLUSION: pAQP1 is the first porcine aquaporin that can be molecularly identified so far. The broad distribution of pAQP1 in epithelium and endothelium of porcine digestive organs may suggest an important role of channel-mediated water transport in fluid secretion/absorption as well as in digestive function and pathophysiology of the gastrointestinal system.
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Affiliation(s)
- Shun-Ying Jin
- Membrane Channel Research Laboratory, Northeast Normal University, 5268 Renmin Street,Changchun 130024, Jilin Province, China
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Lee NPY, Tong MK, Leung PP, Chan VW, Leung S, Tam PC, Chan KW, Lee KF, Yeung WSB, Luk JM. Kidney claudin-19: localization in distal tubules and collecting ducts and dysregulation in polycystic renal disease. FEBS Lett 2006; 580:923-31. [PMID: 16427635 DOI: 10.1016/j.febslet.2006.01.019] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2005] [Revised: 12/09/2005] [Accepted: 01/10/2006] [Indexed: 01/31/2023]
Abstract
Tight junction (TJ) constitutes the barrier by controlling the passage of ions and molecules via paracellular pathway and the movement of proteins and lipids between apical and basolateral domains of the plasma membrane. Claudins, occludin, and junctional adhesion molecules are the major three transmembrane proteins at TJ. This study focuses a newly identified mammalian TJ gene, claudin-19, in kidneys. Mouse claudin-19 composes of 224 amino acids and shares 98.2% and 95% amino acid homology with rat and human, respectively; the most evolutionary-related claudins are claudin-1 and -7, which share approximately 75% DNA sequence homology with claudin-19. Claudin-19 is abundantly expressed in the mouse and rat kidneys among the organs examined by Northern blots, and to a much less extent, also found in brain by RT-PCR. Claudin-19 and zonula occludens-1 (ZO-1) are localized at junctional regions of Madin-Darby canine kidney (MDCK) cells by immunofluorescent microscopy. In addition, ZO-1 is found in the claudin-19-associated protein complexes in MDCK cells by co-immunoprecipitation. Using aquaporin-1 and aquaporin-2 antibodies as markers for different renal segment, strong expression of claudin-19 was observed in distal tubules of the cortex as well as in the collecting ducts of the medulla. To less extent, claudin-19 is also present in the proximal tubules (cortex) and in the loop of Henle (medulla). Furthermore, intense claudin-19 immunoreactivity is found co-localized with the ZO-1 in kidneys from postnatal day 15, day 45, and adult rats and mice. Similar localizations of claudin-19 and ZO-1 are also observed in human kidneys. Since these renal segments are mainly for controlling the paracellular cation transport, it is suggested that claudin-19 may participate in these processes. In human polycystic kidneys, decreased expression and dyslocalization of claudin-19 are noticed, suggesting a possible correlation between claudin-19 and renal disorders. Taken together, claudin-19 is a claudin isoform that is highly and specifically expressed in renal tubules with a putative role in TJ homeostasis in renal physiology.
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Affiliation(s)
- Nikki P Y Lee
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong, SAR, China
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Gao H, He C, Fang X, Hou X, Feng X, Yang H, Zhao X, Ma T. Localization of aquaporin-1 water channel in glial cells of the human peripheral nervous system. Glia 2006; 53:783-7. [PMID: 16534779 DOI: 10.1002/glia.20336] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The aquaporins (AQPs) are a family of water channel proteins with at least 13 mammalian members (AQPs 0-12) expressed in diverse fluid transporting tissues. AQP1, AQP4, and AQP9 have been identified in the central nervous system and demonstrated or proposed to play important roles in brain water homeostasis. Aquaporin expression in the peripheral nervous system is poorly studied. Here we report that the AQP1 water channel is specifically localized to glial cells of the peripheral nervous system by immunohistochemistry, RT-PCR, and immunoblotting. Paraffin-embedded biopsies of human pancreas, esophagus, and sciatic nerves were accessed by immunoperoxidase staining using affinity-purified AQP1, AQP4, and AQP9 antibodies. Strong AQP1 expression was identified in pancreatic nerve plexuses and in the submucosal and myenteric nerve plexuses in the esophagus. AQP1 was localized to the same cell population expressing glial fibrillary acidic protein (GFAP), but not to the neurons in the plexuses, indicating glial cell-specific expression. RT-PCR and immunoblot analysis of microdissected pancreatic ganglia confirmed the expression of AQP1 transcript and protein. Pancreatic and sciatic nerve bundles, which contain nonmyelinating and myelinating Schwann cells, respectively, were also selectively labeled by AQP1 antibody. AQP4 and AQP9, which are broadly expressed in astroglial cells in brain and spinal cord, were not localized in glial cells in the peripheral nerve plexuses. These results suggest that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in peripheral neuronal activity by regulating water homeostasis in nerve plexuses and bundles.
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Affiliation(s)
- Hongwen Gao
- Membrane Channel Research Laboratory, Northeast Normal University, Changchun 130024, PR China
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Abstract
Water homeostasis during fetal development is of crucial physiologic importance. It depends upon maternal fetal fluid exchange at the placenta and fetal membranes, and some exchange between fetus and amniotic fluid can occur across the skin before full keratinization. Lungs only grow and develop normally with fluid secretion, and there is evidence that cerebral spinal fluid formation is important in normal brain development. The aquaporins are a growing family of molecular water channels, the ontogeny of which is starting to be explored. One question that is of particular importance is how well does the rodent (mouse, rat) fetus serve as a model for long-gestation mammals such as sheep and human? This is particularly important for organs such as the lung and the kidney, whose development before birth is very much less in rodents than in the long-gestation species.
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Affiliation(s)
- Huishu Liu
- Guangzhou Obstetric and Gynecology Institute, Second Municipal Hospital of Guangzhou, Guangzhou Medical College, Guangzhou, PR China
| | - E Marelyn Wintour
- Department of Physiology, Monash University, Clayton, Victoria, 3800, Australia
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Motegi K, Azuma M, Tamatani T, Ashida Y, Sato M. Expression of aquaporin-5 in and fluid secretion from immortalized human salivary gland ductal cells by treatment with 5-aza-2'-deoxycytidine: a possibility for improvement of xerostomia in patients with Sjögren's syndrome. J Transl Med 2005; 85:342-53. [PMID: 15640830 DOI: 10.1038/labinvest.3700234] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
The aim of the present study was to investigate the possibility that ductal cells, which preferentially survive and/or proliferate in Sjögren's syndrome (SS) salivary glands of patients with SS, could acquire the functional expression of membrane water channel aquaporin-5 (AQP5). Thus, in this study, we demonstrate that an immortalized normal human salivary gland ductal cell (NS-SV-DC) line, lacking the expression of AQP5, acquires AQP5 gene expression in response to treatment with 5-aza-2'-deoxycytidine (5-Aza-CdR), a DNA demethylating agent. Confocal microscopic analysis revealed the localization of AQP5 expression mainly at the apical and lateral sides of the plasma membrane. The expressed AQP5 protein was functionally active because AQP5 expression resulted in a significant increase in the osmotically directed net fluid rate across monolayers of NS-SV-DC cells. By the analysis of bisulfite sequencing of CpG islands in the AQP5 promoter, hypermethylation within the consensus Sp1-binding sites was commonly observed in parental cell clones, whereas demethylation at the CGs, one in the second consensus Sp1 element and the other outside of the third consensus Sp1 element in the AQP5 promoter, was detected in NS-SV-DC cells after treatment with 5-Aza-CdR. By analyzing the luciferase activity of transfected AQP5 promoter vectors, it became evident that demethylation at the CGs cooperatively functions between these two sites to induce AQP5 expression. Our data, therefore, suggest that treatment of ductal cells with 5-Aza-CdR could result in the expression of the AQP5 gene, thereby leading to increased fluid secretion from ductal cells in SS salivary glands.
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Affiliation(s)
- Katsumi Motegi
- Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima, Japan
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Ohinata A, Nagai K, Nomura J, Hashimoto K, Hisatsune A, Miyata T, Isohama Y. Lipopolysaccharide changes the subcellular distribution of aquaporin 5 and increases plasma membrane water permeability in mouse lung epithelial cells. Biochem Biophys Res Commun 2005; 326:521-6. [PMID: 15596131 DOI: 10.1016/j.bbrc.2004.10.216] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2004] [Indexed: 01/15/2023]
Abstract
Aquaporin-5 (AQP5), a major water channel in lung epithelial cells, plays an important role in maintaining water homeostasis in the lungs. Cell surface expression of AQP5 is regulated by not only mRNA and protein synthesis but also changes in subcellular distribution. We investigated the effect of lipopolysaccharide (LPS) on the subcellular distribution of AQP5 in a mouse lung epithelial cell line (MLE-12). LPS caused significant increases in AQP5 in the plasma membrane at 0.5-2 h. Immunofluorescence and Western blotting strongly suggested that LPS altered AQP5 subcellular distribution from an intracellular vesicular compartment to the plasma membrane. The specific p38 MAP kinase inhibitor SB 203580 apparently prevented LPS-induced changes in AQP5 distribution. Furthermore, LPS increased the osmotic water permeability of MLE-12 cells. These findings demonstrate that LPS increases cell surface AQP5 expression by changing its subcellular distribution and increases membrane osmotic water permeability through activation of p38 MAP kinase.
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Affiliation(s)
- Akira Ohinata
- Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
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Abstract
The determination of the structure of several members of the K+ channel and aquaporin family represents a unique opportunity to explain the mechanism of these biomolecular systems. With their ability to go beyond static structures, molecular dynamics simulations offer a unique route for relating functional properties to membrane channel structure. The recent progress in this area is reviewed.
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Affiliation(s)
- Benoit Roux
- Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA.
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Brañes MC, Morales B, Ríos M, Villalón MJ. Regulation of the immunoexpression of aquaporin 9 by ovarian hormones in the rat oviductal epithelium. Am J Physiol Cell Physiol 2005; 288:C1048-57. [PMID: 15647391 DOI: 10.1152/ajpcell.00420.2003] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The volume of oviductal fluid fluctuates during the estrous cycle, suggesting that water availability is under hormonal control. It has been postulated that sex-steroid hormones may regulate aquaporin (AQP) channels involved in water movement across cell membranes. Using a functional assay (oocytes of Xenopus laevis), we demonstrated that the rat oviductal epithelium contains mRNAs coding for water channels, and we identified by RT-PCR the mRNAs for AQP5, -8, and -9, but not for AQP2 and -3. The immunoreactivity for AQP5, -8, and -9 was localized only in epithelial cells of the oviduct. The distribution of AQP5 and -8 was mainly cytoplasmic, whereas we confirmed, by confocal microscopy, that AQP9 localized to the apical plasma membrane. Staining of AQP5, -8, and -9 was lost after ovariectomy, and only AQP9 immunoreactivity was restored after estradiol and/or progesterone treatments. The recovery of AQP9 reactivity after ovariectomy correlated with increased mRNA and protein levels after treatment with estradiol alone or progesterone administration after estradiol priming. Interestingly, progesterone administration after progesterone priming also induced AQP9 expression but without a change in mRNA levels. Levels of AQP9 varied along the estrous cycle with their highest levels during proestrus and estrus. These results indicate that steroid hormones regulate AQP9 expression at the mRNA and protein level and that other ovarian signals are involved in the expression of AQP5 and -8. Thus hormonal regulation of the type and quantity of water channels in this epithelium might control water transport in the oviductal lumen.
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King LS, Kozono D, Agre P. From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol 2004; 5:687-98. [PMID: 15340377 DOI: 10.1038/nrm1469] [Citation(s) in RCA: 691] [Impact Index Per Article: 32.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Our understanding of the movement of water through cell membranes has been greatly advanced by the discovery of a family of water-specific, membrane-channel proteins - the aquaporins. These proteins are present in organisms at all levels of life, and their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis. The recognition of aquaporins has stimulated a reconsideration of membrane water permeability by investigators across a wide range of disciplines.
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Affiliation(s)
- Landon S King
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, Maryland 21224, USA.
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Hardin JA, Wallace LE, Wong JFK, O'Loughlin EV, Urbanski SJ, Gall DG, MacNaughton WK, Beck PL. Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn's disease and infectious colitis. Cell Tissue Res 2004; 318:313-23. [PMID: 15338270 DOI: 10.1007/s00441-004-0932-4] [Citation(s) in RCA: 87] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2003] [Accepted: 05/26/2004] [Indexed: 12/13/2022]
Abstract
Colitis is associated with alterations in electrolyte and water transport. These changes give rise to some of the symptoms experienced by patients with colitis. Alterations in fluid flux may also contribute to increased susceptibility to mucosal injury. Recently, endogenous water channel proteins (aquaporins; AQPs), have been identified in colonic tissue. The expression of AQP4, AQP7 and AQP8 was examined, via reverse transcription/polymerase chain reaction, Western blotting and immunohistochemistry, in a murine model of colitis and in patients with inflammatory bowel disease or infectious colitis. Colitis was induced in C57BL/6 mice by the addition of 2.5% dextran sodium sulphate (DSS) to their drinking water. AQP expression in these mice was assessed following 12 h to 7 days of DSS exposure and during the recovery phase from 1 to 15 days following cessation of DSS exposure. Colonic water transport was measured after 1 and 3 days of DSS and following 7 days of recovery. The expression of AQP4 and AQP8 mRNA was significantly decreased after 12-24 h of DSS exposure and remained depressed throughout the treatment period. Expression of AQP7 was more variable. Protein expression followed a similar pattern to that observed for AQP mRNA. Significant alteration in colonic fluid secretion was correlated with reduced expression of AQP isoforms. Significantly, patients with active ulcerative colonic, Crohn's colitis or infectious colitis had similar dramatic reductions in AQP expression that appeared to be correlated with disease activity. Thus, colonic injury in both mouse and man is associated with a downregulation in AQP expression.
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Affiliation(s)
- J A Hardin
- The Gastrointestinal Research Unit, University of Calgary, Calgary, AB, Canada
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van Vonderen IK, Wolfswinkel J, van den Ingh TSGAM, Mol JA, Rijnberk A, Kooistra HS. Urinary aquaporin-2 excretion in dogs: a marker for collecting duct responsiveness to vasopressin. Domest Anim Endocrinol 2004; 27:141-53. [PMID: 15219933 DOI: 10.1016/j.domaniend.2004.03.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2004] [Accepted: 03/21/2004] [Indexed: 11/21/2022]
Abstract
In humans, the urinary aquaporin-2 (U-AQP2) excretion closely parallels changes in vasopressin (VP) action and has been proposed as a marker for collecting duct responsiveness to VP. This report describes the development of a radioimmunoassay for the measurement of U-AQP2 excretion in dogs. In addition, the localization of AQP2 in the canine kidney was investigated by immunohistochemistry. Basal U-AQP2 excretion was highly variable among healthy dogs. Two hours after oral water loading, the mean U-AQP2/creatinine ratio decreased significantly from (231 +/- 30) x 10(-9) to (60 +/- 15) x 10(-9) (P = 0.01), while the median plasma VP concentration decreased from 4.2 pmol/l (range 2.2-4.8 pmol/l) to 1.2 pmol/l (range 1.0-1.9 pmol/l). Subsequent intravenous administration of desmopressin led to a significantly increased mean U-AQP2/creatinine ratio of (258 +/- 56) x 10(-9) (P = 0.01). Two hours of intravenous hypertonic saline infusion (20% NaCl, 0.03 ml/kg body weight/min) significantly increased the mean U-AQP2/creatinine ratio from (86 +/- 6) x 10(-9) to (145 +/- 23) x 10(-9) (P = 0.045), while the median plasma VP concentration increased significantly from 2.2 pmol/l (range 1.1-6.3 pmol/l) to 17.1 pmol/l (range 8.4-67 pmol/l) (P < 0.001). Immunohistochemistry revealed extensive labeling for AQP2 in the kidney collecting duct cells, predominantly localized in the apical and subapical region. As in humans, U-AQP2 excretion in dogs closely reflects changes in VP exposure. Urinary AQP2 excretion may become a diagnostic tool in dogs for the differentiation of polyuric conditions such as (partial) central or nephrogenic diabetes insipidus, primary polydipsia, and inappropriate VP release.
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Affiliation(s)
- I K van Vonderen
- Department of Clinical Sciences of Companion Animals, Utrecht University, P.O. Box 80.154, Yalelaan 8, 3508 TD, The Netherlands
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