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Wang Y, Jiang Y, Jiang L, Xiong W, Wang Y, Gao X, Chen Q, Lin L, Yu T, Tang Y. Estrogen increases the expression of BKCa and impairs the contraction of colon smooth muscle via upregulation of sphingosine kinase 1. J Cell Physiol 2023; 238:2390-2406. [PMID: 37642352 DOI: 10.1002/jcp.31106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 06/03/2023] [Accepted: 07/20/2023] [Indexed: 08/31/2023]
Abstract
Estrogen (E2) may impair the contraction of colonic smooth muscle (SM) leading to constipation. Large conductance Ca2+ -activated K+ channels (BKCa ) are widely expressed in the smooth muscle cells (SMCs) contributing to hyperpolarization and relaxation of SMCs. Sphingosine kinase 1 (SphK1) is known to influence the expression of BKCa . We aimed to elucidate the potential underlying molecular mechanism of BKCa and SphK1 that may influence E2-induced colonic dysmotility. In ovariectomized rats, SM contraction and expression of BKCa , SphK1, sphingosine-1-phosphate receptor (S1PR) were analyzed after the treatment with vehicle, BSA-E2, E2, and E2 receptor antagonist. The role of BKCa , SphK1, and S1PR in E2-induced SM dysmotility was investigated in rat colonic SMCs. The effect of SphK1 on SM contraction as well as on the expression of BKCa and S1PR was analyzed in SphK1 knock-out mutant mice and wild-type (WT) mice treated with or without E2. The E2-treated group exhibited a weak contraction of colonic SM and a delayed colonic transit. The treatment with E2 significantly upregulated the expression of BKCa , SphK1, S1PR1, and S1PR2, but not S1PR3, in colon SM and SMCs. Inhibition of BKCa , SphK1, S1PR1, and S1PR2 expression attenuated the effect of E2 on Ca2+ mobilization in rat colon SMCs. WT mice treated with E2 showed impaired gastrointestinal motility and enhanced expression of BKCa , S1PR1, and S1PR2 compared with those without E2 treatment. Conversely, in SphK1 knock-out mice treated with E2, these effects were partially reversed. E2 increased the release of S1P which in turn could have activated S1PR1 and S1PR2. Loss of SphK1 attenuated the effect of E2 on the upregulation of S1PR1 and S1PR2 expression. These findings indicated that E2 impaired the contraction of colon SM through activation of BKCa via the upregulation of SphK1 and the release of S1P. In the E2-induced BKCa upregulation, S1PR1 and S1PR2 might also be involved. These results may provide further insights into a therapeutic target and optional treatment approaches for patients with constipation.
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Affiliation(s)
- Yan Wang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ya Jiang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ling Jiang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wenjie Xiong
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yanjuan Wang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiangyue Gao
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qi Chen
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lin Lin
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ting Yu
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yurong Tang
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Li H, Wang Y, Tian Y, Tian F, Xing Z, Wang Y, Yan M, Gong Y. Atractylodes chinensis volatile oil up-regulated IGF-1 to improve diabetic gastroparesis in rats. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2022; 25:520-526. [PMID: 35656073 PMCID: PMC9150807 DOI: 10.22038/ijbms.2022.60126.13339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 04/09/2022] [Indexed: 11/10/2022]
Abstract
Objectives Diabetic gastroparesis (DGP) is one of the main complications of diabetes, and more than half of diabetes cases are accompanied by gastroparesis. This study aims to explore the effect of Atractylodes chinensis volatile oil (ACVO) on DGP rats. Materials and Methods The rats were injected with STZ combined with a high-sugar and high-fat diet in an irregular manner to establish the DGP model. ACVO at different doses (9.11 mg/kg, 18.23 mg/kg, and 36.45 mg/kg) were given by intragastric administration. A mixture of cisapride and metformin was used as the positive control. At the end of the experiment, gastric emptying and intestinal propulsion were determined. Then the tissue samples and blood were taken from each group for serum analysis, western blot and immunopathological examination. Results After treatment with ACVO, body weight increased and blood glucose decreased when compared with rats in the DGP group. Gastric emptying and intestinal propulsion were accelerated, and gastric acid secretion increased. The serum insulin-like growth factor-1 (IGF-1) level was increased. Protein expressions and positive cells of IGF-1 receptor (IGF-1R), acetylcholine transferase (CHAT), and stem cell factors (SCF) in the stomach were significantly increased determined by western blot and immunofluorescence staining. The morphology and the number of interstitial cells of Cajal (ICCs) in the stomach were restored, determined by hematoxylin and eosin staining and immunohistochemical staining, respectively. Conclusion ACVO effectively alleviated DGP in rats, and its mechanism may be related to the up-regulation of IGF-1/IGF-1R signaling.
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Affiliation(s)
- Hongzeng Li
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China,These authors contributed equally to this work
| | - Yitong Wang
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China,These authors contributed equally to this work
| | - Yuxin Tian
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
| | - Feiyue Tian
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
| | - Zhiyang Xing
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
| | - Yunfei Wang
- Shandong Xinhua Pharmaceutical Company Limited, Zibo, China
| | - Meixing Yan
- Qingdao Women and Children’s Hospital, Qingdao, China,Corresponding authors: Meixing Yan. Qingdao Women and Children’s Hospital, Qingdao 266011, China. ; Yanling Gong, Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, 53 Zhengzhou Road, Qingdao 266042, China.
| | - Yanling Gong
- Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China,Corresponding authors: Meixing Yan. Qingdao Women and Children’s Hospital, Qingdao 266011, China. ; Yanling Gong, Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, 53 Zhengzhou Road, Qingdao 266042, China.
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Differential Expression Profiles and Functional Prediction of circRNAs in Necrotizing Enterocolitis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9862066. [PMID: 34778461 PMCID: PMC8581514 DOI: 10.1155/2021/9862066] [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: 05/16/2021] [Accepted: 10/12/2021] [Indexed: 12/31/2022]
Abstract
Circular RNAs (circRNAs), a novel type of noncoding RNAs, have been demonstrated to behave as microRNA (miRNA) sponges to exert their effects during pathological processes of diseases. However, the roles of circRNAs have not been explored in necrotizing enterocolitis (NEC). This study sought to identify differentially expressed circRNAs and predict their potential biological functions in NEC. circRNA expression profiles in terminal ileum from newborn rats with NEC and normal controls were explored using next-generation sequencing. In the NEC group, 53 circRNAs were significantly differentially expressed, including 9 upregulated and 44 downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted, and circRNA-miRNA interaction networks were generated to predict the potential roles of circRNAs in NEC progression. Further investigation revealed that most circRNAs include miRNA binding sites and that some are implicated in NEC development. In conclusion, this study's findings demonstrate that differentially expressed circRNAs are involved in NEC development via their interactions with miRNAs, making them prospective targets for NEC diagnosis and treatment.
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Shen X, Zhang L, Jiang L, Xiong W, Tang Y, Lin L, Yu T. Alteration of sphingosine-1-phosphate with aging induces contractile dysfunction of colonic smooth muscle cells via Ca 2+ -activated K + channel (BK Ca ) upregulation. Neurogastroenterol Motil 2021; 33:e14052. [PMID: 33452855 DOI: 10.1111/nmo.14052] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 10/13/2020] [Accepted: 11/13/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Age-associated changes alter calcium-activated potassium channel (BKCa ) expression of colon. Sphingolipids (SLs) are important cell membrane structural components; altered composition of SLs may affect BKCa expression. This study investigated the mechanism by which sphingosine-1-phosphate (S1P) contributes to age-associated contractile dysfunction. METHODS Fifty male Sprague Dawley rats of different ages were randomly assigned to five age-groups, namely 3, 6, 12, 18, and 24 months. BKCa expression, S1P levels, and phosphorylated myosin light chain (p-MLC) levels were tested in colonic tissues. In the absence and presence of S1P treatment, BKCa expression, p-MLC levels, and intracellular calcium mobilization were tested in vitro. BKCa small interfering RNA (siRNA) was used to investigate whether p-MLC expression and calcium mobilization were affected by BKCa in colonic smooth muscle cells (SMCs). The expressions of phosphorylated protein kinase B, c-Jun N-terminal kinases (JNKs), extracellular-regulated protein kinases, nuclear factor kappa-B (NF-κB), and protein kinase Cζ (PKCζ ) were examined to investigate the correlation between S1P and BKCa . KEY RESULTS Sphingosine-1-phosphate levels and sphingosine-1-phosphate receptor 2 (S1PR2) and BKCa expressions were upregulated and p-MLC expression was downregulated in the colonic tissues, age dependently. In the cultured SMCs, S1P treatment increased BKCa expression and reduced calcium concentration and p-MLC was observed. BKCa siRNA increased calcium concentration, and p-MLC levels significantly compared with control. We also showed that S1P upregulated BKCa through PKCζ , JNK, and NF-κB pathways. CONCLUSIONS AND INFERENCES In conclusion, S1P and S1PR2 participate in age-associated contractile dysfunction via BKCa upregulation through PKCζ , JNK, and NF-κB pathways.
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Affiliation(s)
- Xiaoxue Shen
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ling Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ling Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wenjie Xiong
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yurong Tang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lin Lin
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ting Yu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Wang W, Sun M, Zheng YL, Sun LY, Qu SQ. Effects of Bifidobacterium infantis on cytokine-induced neutrophil chemoattractant and insulin-like growth factor-1 in the ileum of rats with endotoxin injury. World J Gastroenterol 2019; 25:2924-2934. [PMID: 31249450 PMCID: PMC6589735 DOI: 10.3748/wjg.v25.i23.2924] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 03/12/2019] [Accepted: 03/30/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The digestive tract is the maximal immunizing tissue in the body, and mucosal integrity and functional status of the gut is very important to maintain a healthy organism. Severe infection is one of the most common causes of gastrointestinal dysfunction, and the pathogenesis is closely related to endotoxemia and intestinal barrier injury. Bifidobacterium is one of the main probiotics in the human body that is involved in digestion, absorption, metabolism, nutrition, and immunity. Bifidobacterium plays an important role in maintaining the intestinal mucosal barrier integrity. This study investigated the protective mechanism of Bifidobacterium during ileal injury in rats.
AIM To investigate the effects of Bifidobacterium on cytokine-induced neutrophil chemoattractant (CINC) and insulin-like growth factor 1 (IGF-1) in the ileum of rats with endotoxin injury.
METHODS Preweaning rats were randomly divided into three groups: Control (group C), model (group E) and treatment (group T). Group E was intraperitoneally injected with lipopolysaccharide (LPS) to create an animal model of intestinal injury. Group T was intragastrically administered Bifidobacterium suspension 7 d before LPS. Group C was intraperitoneally injected with normal saline. The rats were killed at 2, 6 or 12 h after LPS or physiological saline injection to collect ileal tissue samples. The expression of ileal CINC mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), and expression of ileal IGF-1 protein and mRNA was detected by immunohistochemistry and RT-PCR, respectively.
RESULTS The ileum of rats in Group C did not express CINC mRNA, ileums from Group E expressed high levels, which was then significantly decreased in Group T (F = 23.947, P < 0.05). There was no significant difference in CINC mRNA expression at different times (F = 0.665, P > 0.05). There was a high level of IGF-1 brown granules in ileal crypts and epithelial cells in Group C, sparse staining in Group E, and dark, dense brown staining in Group T. There was a significant difference between Groups C and E and Groups E and T (P < 0.05). There was no significant difference in IGF-1 protein expression at different times (F = 1.269, P > 0.05). IGF-1 mRNA expression was significantly different among the three groups (P < 0.05), though not at different times (F = 0.086, P > 0.05).
CONCLUSION Expression of CINC mRNA increased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium reduced CINC mRNA expression. IGF-1 protein and mRNA expression decreased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium prevented the decrease in IGF-1 expression. Bifidobacterium may increase IGF-1 expression and enhance intestinal immune barrier function in rats with endotoxin injury.
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Affiliation(s)
- Wei Wang
- Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Mei Sun
- Department of Pediatric Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Yu-Ling Zheng
- Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Liu-Yu Sun
- Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Shu-Qiang Qu
- Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
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He Y, Yuan X, Zhou G, Feng A. Activation of IGF-1/IGFBP-3 signaling by berberine improves intestinal mucosal barrier of rats with acute endotoxemia. Fitoterapia 2018; 124:200-205. [DOI: 10.1016/j.fitote.2017.11.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Revised: 11/06/2017] [Accepted: 11/13/2017] [Indexed: 12/19/2022]
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Yang Z, Xie L, Han L, Qu X, Yang Y, Zhang Y, He Z, Wang Y, Li J. Circular RNAs: Regulators of Cancer-Related Signaling Pathways and Potential Diagnostic Biomarkers for Human Cancers. Theranostics 2017; 7:3106-3117. [PMID: 28839467 PMCID: PMC5566109 DOI: 10.7150/thno.19016] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Accepted: 05/07/2017] [Indexed: 12/14/2022] Open
Abstract
Circular RNAs (circRNAs) are newly discovered endogenous non-coding RNAs featuring structural stability, high abundance, and tissue-specific expression. CircRNAs are prevalent and conserved in mammalian cells. They are involved in cellular processes and regulate gene expression at the transcriptional or post-transcriptional level by interacting with microRNAs (miRNAs) and other molecules. Recent studies have shown that circRNAs play an important role in the progression of various human diseases including atherosclerosis, nervous system disorders, diabetes, and cancer. In this review, we summarize the advances on endogenous circRNAs in eukaryotic cells and elucidate their diagnostic and prognostic significance in human cancers. Especially, we highlight the involvement of circRNAs in signal transduction pathways as well as their clinical potential to serve as biomarkers.
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Study on the mechanisms of electroacupuncture for promoting gastrointestinal motility in rats with diabetic gastroparesis. JOURNAL OF ACUPUNCTURE AND TUINA SCIENCE 2017. [DOI: 10.1007/s11726-017-0994-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Zhao M, Liao D, Zhao J. Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes 2017; 8:249-269. [PMID: 28694926 PMCID: PMC5483424 DOI: 10.4239/wjd.v8.i6.249] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/05/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023] Open
Abstract
The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.
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Yang S, Dong F, Li D, Sun H, Wu B, Sun T, Wang Y, Shen P, Ji F, Zhou D. Persistent distention of colon damages interstitial cells of Cajal through Ca 2+ -ERK-AP-1-miR-34c-SCF deregulation. J Cell Mol Med 2017; 21:1881-1892. [PMID: 28580775 PMCID: PMC5571545 DOI: 10.1111/jcmm.13108] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 01/02/2017] [Indexed: 12/30/2022] Open
Abstract
Gastrointestinal motility disorders (GMDs) are attributed to loss of interstitial cells of Cajal (ICC), whose survival and function are deeply dependent on the activation of KIT/SCF signalling. Based on the facts that gastrointestinal distention is common in GMD patients and SCF produced by smooth muscle cells (SMCs) is usually decreased before ICC loss, we considered a possible contribution of persistent gastrointestinal distention/stretch to SCF deficiency. In this study, chronic colonic distention mouse model, diabetic gastrointestinal paresis mouse model, cultured mouse colonic SMCs and colon specimens from Hirschsprung's disease patients were used. The results showed that SCF was clearly decreased in distent colon of mice and patients, and microRNA array and real-time PCR indicated a concomitant increase of miR-34c in distent colon. A negative regulation of miR-34c on SCF expression was confirmed by luciferase reporter assays together with knock-down and overexpression of miR-34c in cultured colonic SMCs. Using EMSA and ChIP assays, we further consolidated that in response to persistent stretch, the transcription factor AP-1/c-Jun was highly activated in colonic SMCs and significantly promoted miR-34c transcription by binding to miR-34c promoter. Knock-down or overexpression of AP-1/c-Jun in cultured colonic SMCs leads to down- or up-regulation of miR-34c, respectively. In addition, the activation of AP-1/c-Jun was through ERK1/2 signalling provoked by Ca2+ overload in colonic SMCs that were subject to persistent stretch. In conclusion, our data demonstrated that persistent distention/stretch on colonic SMCs could suppress SCF production probably through Ca2+ -ERK-AP-1-miR-34c deregulation, resulting in ICC loss or impairment and GMD progress.
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Affiliation(s)
- Shu Yang
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
| | - Fang Dong
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Dandan Li
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
| | - Haimei Sun
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
| | - Bo Wu
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
| | - Tingyi Sun
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
| | - Yaxi Wang
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Ping Shen
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Fengqing Ji
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
| | - Deshan Zhou
- Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China
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Effect of acupuncture at points selected from different regions on SCF-kit signaling pathway in diabetic gastroparesis rats. JOURNAL OF ACUPUNCTURE AND TUINA SCIENCE 2017. [DOI: 10.1007/s11726-017-0978-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Chen XL, Liu L, Wen QQ, Li P, Wang Y, Wei XR, Yue ZH. Effect of acupuncture at different acupoints on RhoA/ROCK signaling pathway in gastric antral smooth muscle tissue of rats with diabetic gastroparesiws. Shijie Huaren Xiaohua Zazhi 2016; 24:3508-3516. [DOI: 10.11569/wcjd.v24.i23.3508] [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 observe the effect of acupuncture at different acupoints on the RhoA/ROCK signaling pathway in the gastric antrum of diabetic gastroparesis (DGP) rats.
METHODS: Sixty SD rats were randomly divided into a normal group, a model group, a Zusanli + Zhongwan group, a Zusanli + Neiguan, and a Zusanli + non-acupoint group, with 12 rats in each group. DGP was indueced by intraperitoneal injection of streptozotocin, followed by feeding for 8 wk. After 4 wk of treatment, the gastrointestinal transit rate was measured with black ink. The expression of RhoA protein and ROCK protein was detected by immunohistochemistry and Western blot.
RESULTS: Compared with the normal group, the model group showed a significant reduction in gastrointestinal transit rate and expression of RhoA, ROCK, MYPT1, and p-MYPT1 in gastric antral smooth muscle tissue and a significant increase in RhoA expression (P < 0.01), suggesting that DGP was successfully induced. Compared with the model group, the gastrointestinal transit rate and expression of RhoA, ROCK, MYPT1 and p-MYPT1 in gastric antrum tissue significantly increased in the Zusanli + Zhongwan, Zusanli + Neiguan and Zusanli + non-acupoint groups (P < 0.05). RhoA, ROCK, MYPT1 and p-MYPT1 expression was significantly higher in the Zusanli + Zhongwan group than in the Zusanli + Neiguan and Zusanli + non-acupoint groups (P < 0.05). RhoA expression in gastric antral smooth muscle tissue was significantly higher in the Zusanli + Neiguan and Zusanli + non-acupoint groups than in the Zusanli + Zhongwan group (P < 0.05). The dietary intake was significantly reduced in the Zusanli + Zhongwan group compared with the model group during the treatment period (P < 0.05).
CONCLUSION: Acupoint selection is an important factor to influence the effect of acupoint compatibility. Combination of local acupoints is obviously superior to the compatibility of distal acupoints and non-acupoint.
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Li H, Chen Y, Liu S, Hou XH. Long-pulse gastric electrical stimulation protects interstitial cells of Cajal in diabetic rats via IGF-1 signaling pathway. World J Gastroenterol 2016; 22:5353-5363. [PMID: 27340351 PMCID: PMC4910656 DOI: 10.3748/wjg.v22.i23.5353] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Revised: 04/14/2016] [Accepted: 05/04/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of different parameters of gastric electrical stimulation (GES) on interstitial cells of Cajal (ICCs) and changes in the insulin-like growth factor 1 (IGF-1) signal pathway in streptozotocin-induced diabetic rats. METHODS Male rats were randomized into control, diabetic (DM), diabetic with sham GES (DM + SGES), diabetic with GES1 (5.5 cpm, 100 ms, 4 mA) (DM + GES1), diabetic with GES2 (5.5 cpm, 300 ms, 4 mA) (DM + GES2) and diabetic with GES3 (5.5 cpm, 550 ms, 2 mA) (DM + GES3) groups. The expression levels of c-kit, M-SCF and IGF-1 receptors were evaluated in the gastric antrum using Western blot analysis. The distribution of ICCs was observed using immunolabeling for c-kit, while smooth muscle cells and IGF-1 receptors were identified using α-SMA and IGF-1R antibodies. Serum level of IGF-1 was tested using enzyme-linked immunosorbent assay. RESULTS Gastric emptying was delayed in the DM group but improved in all GES groups, especially in the GES2 group. The expression levels of c-kit, M-SCF and IGF-1R were decreased in the DM group but increased in all GES groups. More ICCs (c-kit(+)) and smooth muscle cells (α-SMA(+)/IGF-1R(+)) were observed in all GES groups than in the DM group. The average level of IGF-1 in the DM group was markedly decreased, but it was up-regulated in all GES groups, especially in the GES2 group. CONCLUSION The results suggest that long-pulse GES promotes the regeneration of ICCs. The IGF-1 signaling pathway might be involved in the mechanism underlying this process, which results in improved gastric emptying.
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Wang XQ, Hu MM, Wang W, Gao F, Zhang LM, Yan FY, Ju J. Pathogenesis of diabetic gastrointestinal dysfunction. Shijie Huaren Xiaohua Zazhi 2016; 24:2682-2687. [DOI: 10.11569/wcjd.v24.i17.2682] [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
Diabetic gastrointestinal dysfunction is a common complication in patients with diabetes mellitus. Most of the symptoms are related to impaired gastrointestinal function. The pathogenesis and etiology of diabetic gastroenteropathy are complex, involving the parasympathetic and sympathetic nervous systems, enteric neurons, smooth muscle cells, the network of interstitial cells of Cajal, cholinergic receptors and neuronal nitric oxide synthase. This article reviews the pathogenesis of diabetic gastrointestinal dysfunction.
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Liu L, Chen XL, Wen QQ, Li P, Wei XR, Wang Y, Yue ZH. Effects of acupuncture at different acupoints on c-fos and glial fibrillary acidic protein expression in the medulla oblongata of rats with diabetic gastroparesis. Shijie Huaren Xiaohua Zazhi 2016; 24:1701-1707. [DOI: 10.11569/wcjd.v24.i11.1701] [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 observe the effects of acupuncture at different acupoints on the expression of c-fos and glial fibrillary acidic protein (GFAP) in the medulla oblongata of rats with diabetic gastroparesis (DGP), and to discuss whether the ministry of acupoints is the factor influencing the effect of acupoints compatibility.
METHODS: Sixty SD rats were randomly divided into a normal group, a model group, a Zusanli + Zhongwan group, a Zusanli + Neiguan group, and a Zusanli + non acupoint group, with 12 rats in each group. DGP was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg, 2%) and treated for 4 wk continuously. After treatment, small intestinal transit rate was measured with black ink, and the expression of c-fos and GFAP in the medulla oblongata was detected by immunohistochemistry.
RESULTS: In comparison with the normal control group, small intestinal transit rate of the model group was significantly decreased, and the gray values of c-fos and GFAP were decreased (P < 0.05). In comparison with the model group, small intestinal transit rates of the Zusanli + Zhongwan group, Zusanli + Neiguan group, and Zusanli + non acupoint group were significantly increased, and the gray values of c-fos and GFAP were significantly increased (P < 0.05). In comparison with the Zusanli + Zhongwan group, the gray values of c-fos and GFAP in the Zusanli + Neiguan group and Zusanli + non acupoint group were significantly decreased (P < 0.05).
CONCLUSION: Acupuncture can improve the symptoms of delayed gastric emptying in DGP rats, and regulate the expression of c-fos and GFAP in the medulla. The compatibility of local acupoints is significantly better than the compatibility of distal acupoints and nonpoints. Acupoint selection is the key factor affecting acupoint compatibility.
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Coleski R, Wilding GE, Semler JR, Hasler WL. Blunting of Colon Contractions in Diabetics with Gastroparesis Quantified by Wireless Motility Capsule Methods. PLoS One 2015; 10:e0141183. [PMID: 26510137 PMCID: PMC4624915 DOI: 10.1371/journal.pone.0141183] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2015] [Accepted: 10/06/2015] [Indexed: 12/12/2022] Open
Abstract
Generalized gut transit abnormalities are observed in some diabetics with gastroparesis. Relations of gastric emptying abnormalities to colon contractile dysfunction are poorly characterized. We measured colon transit and contractility using wireless motility capsules (WMC) in 41 healthy subjects, 12 diabetics with gastroparesis (defined by gastric retention >5 hours), and 8 diabetics with normal gastric emptying (≤5 hours). Overall numbers of colon contractions >25 mmHg were calculated in all subjects and were correlated with gastric emptying times for diabetics with gastroparesis. Colon transit periods were divided into quartiles by time and contraction numbers were calculated for each quartile to estimate regional colon contractility. Colon transit in diabetics with gastroparesis was prolonged vs. healthy subjects (P<0.0001). Overall numbers of colon contractions in gastroparetics were lower than controls (P = 0.02). Diabetics with normal emptying showed transit and contraction numbers similar to controls. Gastric emptying inversely correlated with overall contraction numbers in gastroparetics (r = -0.49). Numbers of contractions increased from the 1st to 4th colon transit quartile in controls and diabetics with normal emptying (P≤0.04), but not gastroparetics. Numbers of contractions in the 3rd and 4th quartiles were reduced in gastroparetics vs. healthy controls (P≤0.05) and in the 4th quartile vs. diabetics with normal emptying (P = 0.02). Numbers of contractions were greatest in the final 15 minutes of transit, but were reduced in gastroparetics vs. healthy controls and diabetics with normal emptying (P≤0.005). On multivariate analyses, differences in numbers of contractions were not explained by demographic or clinical variables. In conclusion, diabetics with gastroparesis exhibit delayed colon transit associated with reductions in contractions that are prominently blunted in latter transit phases and which correlate with delayed gastric emptying, while diabetics with normal emptying show no significant colonic impairments. These findings emphasize diabetic gastroparesis may be part of a generalized dysmotility syndrome.
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Affiliation(s)
- Radoslav Coleski
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, United States of America
| | - Gregory E. Wilding
- Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, United States of America
| | - John R. Semler
- Medtronic, Sunnyvale, California, United States of America
| | - William L. Hasler
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, United States of America
- * E-mail:
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Sun M, Wang F, Feng P. Insulin-like growth factor-1 inhibits colonic smooth muscle cell apoptosis in diabetic rats with colonic dysmotility. ACTA ACUST UNITED AC 2014; 194-195:41-8. [PMID: 25450576 DOI: 10.1016/j.regpep.2014.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2014] [Revised: 11/04/2014] [Accepted: 11/11/2014] [Indexed: 02/08/2023]
Abstract
Cellular apoptosis and colonic dysmotility are involved in diabetes mellitus (DM) complications. Insulin-like growth factor-1 (IGF-1) is known to affect apoptosis and proliferation. Here, we demonstrated that the treatment of 1500 ng/kg IGF-1 partly recovers the decrease of the muscle thickness, body weight and gastrointestinal transit rate in DM rats. The gastrointestinal transit rate is positively correlated with the IGF-I level, but negatively correlated with the level of colonic cellular apoptosis. The DM-induced colonic apoptosis is also attenuated by the IGF-1 stimulation. Moreover, IGF-1 inhibits the apoptosis of the isolated colonic SMCs in vitro via the activation of PI3K/Akt and ERK1/2 signaling pathways. Taken together, our data indicated that IGF-1 inhibits the DM-induced colonic SMC apoptosis and might be involved in the alleviation of colonic dysmotility in diabetic rats.
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Affiliation(s)
- Manyi Sun
- Department of Metabolic Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Gastroenterology, Tianjin Union Medicine Center, Tianjin 300121, China
| | - Feng Wang
- Department of Gastroenterology and Digestive Endoscopy, Tianjin Union Medicine Center & Tianjin People's Hospital, Tianjin 300121, China
| | - Ping Feng
- Department of Metabolic Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China.
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Wu QX, Zhao M, Tan ZR, Qin LR, Huang X, Zhang HJ. Changes of interstitial cells of Cajal and connexin 43 expression in the gastric antrum of rats with diabetic gastroparesis: Implications for interventional effect of insulin. Shijie Huaren Xiaohua Zazhi 2014; 22:4399-4405. [DOI: 10.11569/wcjd.v22.i29.4399] [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 observe the alterations of interstitial cells of Cajal (ICC) and connexin 43 (Cx43) in gastric antrum tissue of a rat model of diabetic gastroparesis (DGP) and assess the interventional effect of insulin.
METHODS: Sprague-Dawley rats were randomly divided into a diabetic model group, a normal control group and an insulin intervention group. Diabetes was induced by intra-peritoneal injection of streptozotocin. Gastric emptying was measured, and the expression of ICC and Cx43 in the gastric antrum was analyzed by immunohistochemistry. The alterations of the ultrastructure of ICC and gap junction were observed by transmission electron microscopy (TEM) at the 10th week after modeling.
RESULTS: Blood glucose and body weight in the diabetic model group were significantly different from those in other groups. The gastric pigment remnant rate was significantly increased in the diabetic model group. Immunohistochemical staining showed that in diabetic rats, the number of ICC in the circular and longitudinal muscle layers decreased and Cx43 was lowly expressed in circular muscle layers. TEM showed organelle degeneration, cytoplasm dissolution and loosening of the structure of gap junction. Insulin could decrease the gastric pigment remnant rate, increase the number of ICC and Cx43 expression, and reverse ultrastructural changes.
CONCLUSION: The decrease of ICC expression and Cx43 expression might be one of the mechanisms responsible for DGP. Insulin can increase the expression of ICC and Cx43 and thus improve gastrointestinal disorders.
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