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Wang H, Gao L, Zhao C, Fang F, Liu J, Wang Z, Zhong Y, Wang X. The role of PI3K/Akt signaling pathway in chronic kidney disease. Int Urol Nephrol 2024; 56:2623-2633. [PMID: 38498274 DOI: 10.1007/s11255-024-03989-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 02/12/2024] [Indexed: 03/20/2024]
Abstract
Chronic kidney disease (CKD), including chronic glomerulonephritis, IgA nephropathy and diabetic nephropathy, are common chronic diseases characterized by structural damage and functional decline of the kidneys. The current treatment of CKD is symptom relief. Several studies have reported that the phosphatidylinositol 3 kinases (PI3K)/protein kinase B (Akt) signaling pathway is a pathway closely related to the pathological process of CKD. It can ameliorate kidney damage by inhibiting this signal pathway which is involved with inflammation, oxidative stress, cell apoptosis, epithelial mesenchymal transformation (EMT) and autophagy. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in CKD-induced inflammatory response, apoptosis, autophagy and EMT. We also summarize the latest evidence on treating CKD by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of CKD, and identify potential challenges in developing these clinical therapeutic CKD strategies, and provide appropriate solutions.
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Affiliation(s)
- Hongshuang Wang
- Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China
| | - Lanjun Gao
- Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China
| | - Chenchen Zhao
- Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China
| | - Fang Fang
- Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China
| | - Jiazhi Liu
- Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, 050091, China
| | - Zheng Wang
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns Research, Shijiazhuang, 050091, China
- Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Yan Zhong
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns Research, Shijiazhuang, 050091, China.
- Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.
| | - Xiangting Wang
- Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns Research, Shijiazhuang, 050091, China.
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Aghaei-Zarch SM. Crosstalk between MiRNAs/lncRNAs and PI3K/AKT signaling pathway in diabetes mellitus: Mechanistic and therapeutic perspectives. Noncoding RNA Res 2024; 9:486-507. [PMID: 38511053 PMCID: PMC10950585 DOI: 10.1016/j.ncrna.2024.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 12/24/2023] [Accepted: 01/09/2024] [Indexed: 03/22/2024] Open
Abstract
Diabetes as a fastest growing diseases worldwide is characterized by elevated blood glucose levels. There's an enormous financial burden associated with this endocrine disorder, with unequal access to health care between developed and developing countries. PI3Ks (phosphoinositide 3-kinases) have been demonstrated to be crucial for glucose homeostasis, and malfunctioning of these molecules can contribute to an increase in glucose serum levels, the main pathophysiological feature of diabetes. Additionally, recent evidence suggests that miRNAs and lncRNAs are reciprocally interacting with this signaling pathway. It is therefore evident that abnormal regulation of miRNAs/lncRNAs in the lncRNAs/miRNAs/PI3K/AKT axis is related to clinicopathological characteristics and plays a crucial role in the regulation of biological processes. It has therefore been attempted in this review to describe the interaction between PI3K/AKT signaling pathway and various miRNAs/lncRNAs and their importance in DM biology. We also presented the clinical applications of PI3K/AKT-related ncRNAs/herbal medicine in patients with DM.
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Affiliation(s)
- Seyed Mohsen Aghaei-Zarch
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Wu QS, Zheng DN, Ji C, Qian H, Jin J, He Q. MicroRNA-630 alleviates inflammatory reactions in rats with diabetic kidney disease by targeting toll-like receptor 4. World J Diabetes 2024; 15:488-501. [PMID: 38591087 PMCID: PMC10999043 DOI: 10.4239/wjd.v15.i3.488] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 01/06/2024] [Accepted: 01/29/2024] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Diabetic kidney disease (DKD) is a major complication of diabetes mellitus. Renal tubular epithelial cell (TEC) damage, which is strongly associated with the inflammatory response and mesenchymal trans-differentiation, plays a significant role in DKD; However, the precise molecular mechanism is unknown. The recently identified microRNA-630 (miR-630) has been hypothesized to be closely associated with cell migration, apoptosis, and autophagy. However, the association between miR-630 and DKD and the underlying mechanism remain unknown. AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats. METHODS Streptozotocin was administered to six-week-old male rats to create a hyperglycemic diabetic model. In the second week of modeling, the rats were divided into control, DKD, negative control of lentivirus, and miR-630 overexpression groups. After 8 wk, urine and blood samples were collected for the kidney injury assays, and renal tissues were removed for further molecular assays. The target gene for miR-630 was predicted using bioinformatics, and the association between miR-630 and toll-like receptor 4 (TLR4) was confirmed using in vitro investigations and double luciferase reporter gene assays. Overexpression of miR-630 in DKD rats led to changes in body weight, renal weight index, basic blood parameters and histopathological changes. RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD (P < 0.05). The miR-630 and TLR4 expressions in rat renal TECs (NRK-52E) were measured using quantitative reverse transcription polymerase chain reaction. The mRNA expression level of miR-630 was significantly lower in the high-glucose (HG) and HG + mimic negative control (NC) groups than in the normal glucose (NG) group (P < 0.05). In contrast, the mRNA expression level of TLR4 was significantly higher in these groups (P < 0.05). However, miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Furthermore, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 were significantly higher in the HG and HG + mimic NC groups than in NG group (P < 0.05). However, the levels of these cytokines were significantly lower in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Notably, changes in protein expression were observed. The HG and HG + mimic NC groups showed a significant decrease in E-cadherin protein expression, whereas TLR4, α-smooth muscle actin (SMA), and collagen IV protein expression increased (P < 0.05). Conversely, the HG + miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4, α-SMA, and collagen IV protein expression than in the HG + mimic NC group (P < 0.05). The miR-630 targets TLR4 gene expression. In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC. Additionally, rats treated with miR-630 agomir showed significant reductions in urinary albumin, blood glucose, TLR4, and proinflammatory markers (TNF-α, IL-1β, and IL-6) expression levels (P < 0.05). Moreover, these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells. CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4, and has a protective effect on DKD.
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Affiliation(s)
- Qi-Shun Wu
- Graduate School, Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China
- Department of Nephrology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou 314408, Zhejiang Province, China
- Department of Nephrology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Dan-Na Zheng
- Graduate School, Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China
- Department of Nephrology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou 314408, Zhejiang Province, China
- Department of Nephrology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 314408, Zhejiang Province, China
| | - Cheng Ji
- Molecular Inspection Laboratory, School of Medicine, Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Hui Qian
- Molecular Inspection Laboratory, School of Medicine, Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
| | - Juan Jin
- Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou 310060, Zhejiang Province, China
| | - Qiang He
- Graduate School, Medical College of Soochow University, Suzhou 215006, Jiangsu Province, China
- Department of Nephrology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou 314408, Zhejiang Province, China
- Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou 310060, Zhejiang Province, China
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Liu J, Chen H, Li X, Song C, Wang L, Wang D. Micro-Executor of Natural Products in Metabolic Diseases. Molecules 2023; 28:6202. [PMID: 37687031 PMCID: PMC10488769 DOI: 10.3390/molecules28176202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 09/10/2023] Open
Abstract
Obesity, diabetes, and cardiovascular diseases are the major chronic metabolic diseases that threaten human health. In order to combat these epidemics, there remains a desperate need for effective, safe, and easily available therapeutic strategies. Recently, the development of natural product research has provided new methods and options for these diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are key regulators of metabolic diseases, and natural products can improve lipid and glucose metabolism disorders and cardiovascular diseases by regulating the expression of miRNAs. In this review, we present the recent advances involving the associations between miRNAs and natural products and the current evidence showing the positive effects of miRNAs for natural product treatment in metabolic diseases. We also encourage further research to address the relationship between miRNAs and natural products under physiological and pathological conditions, thus leading to stronger support for drug development from natural products in the future.
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Affiliation(s)
- Jinxin Liu
- Food and Pharmacy College, Xuchang University, Xuchang 461000, China; (J.L.); (C.S.)
| | - Huanwen Chen
- Center for Agricultural and Rural Development, Zhangdian District, Zibo 255000, China;
| | - Xiaoli Li
- Zibo Digital Agriculture and Rural Development Center, Zibo 255000, China;
| | - Chunmei Song
- Food and Pharmacy College, Xuchang University, Xuchang 461000, China; (J.L.); (C.S.)
| | - Li Wang
- School of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, China
| | - Deguo Wang
- Food and Pharmacy College, Xuchang University, Xuchang 461000, China; (J.L.); (C.S.)
- Key Laboratory of Biomarker Based Rapid-Detection Technology for Food Safety of Henan Province, Xuchang University, Xuchang 461000, China
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Shi L, Deng Y, Luo D, Li L, Kuang X, Qi A, Fu B. Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation. Medicine (Baltimore) 2023; 102:e34446. [PMID: 37478256 PMCID: PMC10662869 DOI: 10.1097/md.0000000000034446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 06/30/2023] [Indexed: 07/23/2023] Open
Abstract
This study aimed to explore the possible mechanisms of Ling Gui Zhu Gan decoction (LGZGD) in the treatment of nephrotic syndrome (NS) using network pharmacology combined with molecular docking and molecular dynamics simulation. The active ingredients of LGZGD and their targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Swiss Target Prediction database. The NS targets were retrieved from Genecards, OMIM and Drugbank databases. Next, the intersecting targets of drug and disease were imported into the String database for protein-protein interaction network analysis, and the core targets were identified through topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed in the Metascape platform. Finally, molecular docking and molecular dynamics simulation were performed for further validation. The network analysis showed that 109 active ingredients of LGZGD were associated with 105 targets in NS. The key active ingredients (quercetin, kaempferol, naringenin, licochalcone A, formononetin, beta-sitosterol) and the core targets (IL6, AKT1, TNF, VEGFA, TP53, JUN, IL1B, CASP3, EGFR, and STAT3) were further identified. Enrichment analysis indicated that multiple biological processes and pathways, including AGE-RAGE, PI3K-Akt, JAK-STAT, and HIF-1 signaling pathways, might be regulated by LGZGD in the treatment of NS. Molecular docking and molecular dynamics simulation results further indicated that the key active ingredients of LGZGD could stably bind to the core targets through hydrogen bonding and hydrophobic interaction. This study demonstrates that the active ingredients of LGZGD may regulate multiple targets, biological processes and signaling pathways in NS. Our findings may provide a theoretical basis for further studies on LGZGD in the treatment of NS.
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Affiliation(s)
- Li Shi
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Yuanjun Deng
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Denggui Luo
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Lei Li
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Xuyi Kuang
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Airong Qi
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
| | - Bo Fu
- The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
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Wan X, Liao J, Lai H, Zhang S, Cui J, Chen C. Roles of microRNA-192 in diabetic nephropathy: the clinical applications and mechanisms of action. Front Endocrinol (Lausanne) 2023; 14:1179161. [PMID: 37396169 PMCID: PMC10309560 DOI: 10.3389/fendo.2023.1179161] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 05/25/2023] [Indexed: 07/04/2023] Open
Abstract
Diabetic nephropathy (DN) is one of the most common and intractable microvascular complications of diabetes worldwide, serving as the main cause of terminal renal disease. Due to the lack of early specific symptoms and diagnostic markers, DN severely threatens the sufferer's life. MicroRNA-192 (miR-192) was early identified in human renal cortical tissue and stored and excreted in urine as microvesicles. MiR-192 was found to be involved in the development of DN. For the first time, the present review summarized all the current evidence on the topic of the roles of miR-192 in DN. Finally, 28 studies (ten clinical trials and eighteen experimental studies) were eligible for thorough reviewing. Most of the clinical trials (7/10, 70%) indicated miR-192 might be a protective factor for DN development and progression, while the majority of experimental studies (14/18, 78%) suggested miR-192 might be a pathogenic factor for DN. Mechanistically, miR-192 interacts with various direct targeted proteins (i.e., ZEB1, ZEB2, SIP1, GLP1R, and Egr1) and signaling cascades (i.e., SMAD/TGF-β and PTEN/PI3K/AKT), together contribute to the pathogenesis of DN through epithelial-to-mesenchymal transition (EMT), extracellular matrix deposition, and fibrosis formation. The current review highlights the dual role of miR-192 in the development of DN. Low serum miR-192 expression could be applied for the early prediction of DN (the early stage of DN), while the high miR-192 level in renal tissues and urine may imply the progression of DN (the late stage of DN). Further investigations are still warranted to illustrate this inconsistent phenomenon, which may facilitate promoting the therapeutic applications of miR-192 in predicting and treating DN.
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Affiliation(s)
- Xiaoqing Wan
- Department of Nephrology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Jian Liao
- Department of Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, China
| | - Hongting Lai
- Clinical Medical College, Tianjin Medical University, Tianjin, China
| | - Shilong Zhang
- Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Jianling Cui
- Department of Nephrology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Chunyan Chen
- Department of Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, China
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Zhang PP, Zhuo BY, Duan ZW, Li X, Huang SL, Cao Q, Zhao T, Wei SL, Hu XH, Zhang Y. Marein reduces lipid levels via modulating the PI3K/AKT/mTOR pathway to induce lipophagy. JOURNAL OF ETHNOPHARMACOLOGY 2023; 312:116523. [PMID: 37080364 DOI: 10.1016/j.jep.2023.116523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/04/2023] [Accepted: 04/18/2023] [Indexed: 05/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The capitulum of Coreopsis tinctoria Nutt. (CT, Xue-Ju in Chinese) is a precious medicine in Xinjiang Uygur Autonomous region of China. The Coreopsis tinctoria Nutt. is used to prevent and treat dyslipidemia, coronary heart disease, etc. Recent studies have shown that its extract has a pharmacological effect on hyperlipidemia and hyperglycemia. AIM OF THE STUDY The study aimed to systematically evaluate the lipid-lowering activity of CT through a mice model of hyperlipidemia and a human hepatoma G2 (HepG2) cells model of lipid accumulation, and to investigate its main active components and mechanism. MATERIALS AND METHODS Biochemical analysis of blood/liver lipids and liver histopathology were used to evaluate the effect of the aqueous extract of Coreopsis tinctoria Nutt. (AECT) on hyperlipidemia mice. High-performance liquid chromatography (HPLC) analysis was used to identify the main components in the AECT. Oil red O staining, immunofluorescence, western blotting, and determination of the total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to further study the effect and potential mechanism of the AECT main components on sodium oleate-induced lipid accumulation in HepG2 cells. RESULTS We confirmed the lipid-lowering activity of the aqueous extract and further identified flavonoids as its main components. Among them, five Coreopsis tinctoria Nutt. flavonoids mixture (FM) significantly reduced lipid droplet area, lipid content, TC, TG, and LDL-C levels, and elevated HDL-C levels in HepG2 cells induced by sodium oleate. Furthermore, they increased lipophagy in HepG2 lipid-accumulating cells, while decreasing the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Most importantly, marein may be a key component. CONCLUSIONS Our study demonstrated that AECT, with flavonoids as the main component, can improve diet-induced hyperlipidemia in obese mice. Among the main five flavonoids, marein plays a key role in promoting lipophagy by regulating the PI3K/AKT/mTOR pathway, resulting in a lipid-lowering effect.
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Affiliation(s)
- Pei-Pei Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
| | - Bing-Yu Zhuo
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
| | - Zi-Wei Duan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
| | - Xin Li
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
| | - Song-Li Huang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China.
| | - Qian Cao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
| | - Ting Zhao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China; Engineering Research Center of Good Agricultural Practice for Chinese Crude Drugs, Ministry of Education, Beijing, 100102, China.
| | - Sheng-Li Wei
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China; Engineering Research Center of Good Agricultural Practice for Chinese Crude Drugs, Ministry of Education, Beijing, 100102, China.
| | - Xiu-Hua Hu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China; Engineering Research Center of Good Agricultural Practice for Chinese Crude Drugs, Ministry of Education, Beijing, 100102, China.
| | - Yuan Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China; Engineering Research Center of Good Agricultural Practice for Chinese Crude Drugs, Ministry of Education, Beijing, 100102, China.
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Yu H, Zhang X, Wang X, Chen W, Lao W, Chen Y. MiR-99a-5p Inhibits the Proliferation and Migration of Human Retinal Microvascular Endothelial Cells by Targeting NOX4. Horm Metab Res 2023; 55:142-148. [PMID: 36630972 DOI: 10.1055/a-1982-3926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Diabetic retinopathy is one of the common microvascular complications of diabetes, and it is the main cause of vision loss among working-age people. This study interpreted the roles of miR-99a-5p in DR patients and human retinal microvascular endothelial cell (hRMECs) injury induced by high glucose. The expression of miR-99a-5p was detected in patients with NDR, NPDR, and PDR. The indictive impacts of miR-99a-5p were tested by the ROC curve, and the link between miR-99a-5p and clinical information was verified by the Pearson test. HG was used to instruct cell models. The CCK-8 and transwell methods were performed to detect the proliferative and migrated cells. The targeted relationship was explained by luciferase activity. The content of miR-99a-5p was gradually lessened in NPDR and PDR patients. MiR-99a-5p might differentiate DR patients from NDR patients and PDR patients from NPDR patients. The interconnection between miR-99a-5p and clinical factors was endorsed in all DR patients. Overexpression of miR-99a-5p assuaged the abnormality of cell migration and proliferation of hRMECs triggered by HG. NOX4 was a downstream signaling component of miR-99a-5p. In conclusion, MiR-99a-5p protected hRMECs against HG damage, and the miR-99a-5p might be a novel target for diagnosis of DR.
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Affiliation(s)
- Haizhen Yu
- Department of Clinical Laboratory, Zhucheng People's Hospital, Weifang, China
| | - Xu Zhang
- Department of Ophthalmology, Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xuyang Wang
- Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Opthalmic Center, Sun Yat-sen University, Haikou, Hainan, China
| | - Wangling Chen
- Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Opthalmic Center, Sun Yat-sen University, Haikou, Hainan, China
| | - Wei Lao
- Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Opthalmic Center, Sun Yat-sen University, Haikou, Hainan, China
| | - Yunxin Chen
- Hainan Eye Hospital and Key Laboratory of Ophthalmology, Zhongshan Opthalmic Center, Sun Yat-sen University, Haikou, Hainan, China
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Chen DQ, Wu J, Li P. Therapeutic mechanism and clinical application of Chinese herbal medicine against diabetic kidney disease. Front Pharmacol 2022; 13:1055296. [PMID: 36408255 PMCID: PMC9669587 DOI: 10.3389/fphar.2022.1055296] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 10/24/2022] [Indexed: 12/25/2023] Open
Abstract
Diabetic kidney disease (DKD) is the major complications of type 1 and 2 diabetes, and is the predominant cause of chronic kidney disease and end-stage renal disease. The treatment of DKD normally consists of controlling blood glucose and improving kidney function. The blockade of renin-angiotensin-aldosterone system and the inhibition of sodium glucose cotransporter 2 (SGLT2) have become the first-line therapy of DKD, but such treatments have been difficult to effectively block continuous kidney function decline, eventually resulting in kidney failure and cardiovascular comorbidities. The complex mechanism of DKD highlights the importance of multiple therapeutic targets in treatment. Chinese herbal medicine (active compound, extract and formula) synergistically improves metabolism regulation, suppresses oxidative stress and inflammation, inhibits mitochondrial dysfunction, and regulates gut microbiota and related metabolism via modulating GLP-receptor, SGLT2, Sirt1/AMPK, AGE/RAGE, NF-κB, Nrf2, NLRP3, PGC-1α, and PINK1/Parkin pathways. Clinical trials prove the reliable evidences for Chinese herbal medicine against DKD, but more efforts are still needed to ensure the efficacy and safety of Chinese herbal medicine. Additionally, the ideal combined therapy of Chinese herbal medicine and conventional medicine normally yields more favorable benefits on DKD treatment, laying the foundation for novel strategies to treat DKD.
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Affiliation(s)
- Dan-Qian Chen
- Department of Emergency, China-Japan Friendship Hospital, Beijing, China
| | - Jun Wu
- Shandong College of Traditional Chinese Medicine, Yantai, Shandong, China
| | - Ping Li
- Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
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Fufang Fanshiliu Decoction Revealed the Antidiabetic Effect through Modulating Inflammatory Response and Gut Microbiota Composition. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:3255401. [PMID: 36262166 PMCID: PMC9576391 DOI: 10.1155/2022/3255401] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 08/23/2022] [Accepted: 09/15/2022] [Indexed: 11/07/2022]
Abstract
Background Diabetes mellitus brings serious threats and financial burdens to human beings worldwide. Fufang Fanshiliu decoction (FFSLD), a traditional Chinese medicine formula showing great antidiabetic effects, has been used in clinics for many years. Objective This study aims to explore the underlying therapeutic mechanisms of FFSLD in Type II diabetes mellitus (T2DM). Methods Sprague–Dawley rats induced by high-fat diet feeding combined with streptozotocin injection were used to establish the T2DM model. All rats were randomly divided into 6 groups: control, model, metformin, high dosage, middle dosage, and low dosage of FFSLD. After 4 weeks of treatment, serum, intestinal mucosa, and fecal samples were collected for further analysis. ELISA was used to detect the diabetic-related serum indicators and proinflammation cytokines. Gene or protein expressions of mitogen-activated protein kinase (MAPK), interleukin 1 beta (IL-1β), transforming growth factor-beta (TGF-β), and tumor necrosis factor-alpha (TNF-α) in intestinal mucosa were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) or western blot. 16s rRNA gene sequencing was used to detect the changes of gut microbiome in these groups. Intestinal gut microbiota (GM) composition was further analyzed according to the sequencing libraries. Results FFSLD effectively recovered the diabetic-related biochemical indexes by reducing fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), insulin, and increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, FFSLD significantly ameliorated the abnormal levels of proinflammation cytokines including IL-1β, IL-6, TNF-α, and TGF-β. In addition, the GM compositions of rats in control, model, and FFSLD treated groups were different. FFSLD significantly increased the relative abundance of Lactobacillus, Akkermansia, and Proteus, and reduced the relative abundance of Alistipes, Desulfovibrio, and Helicobacter. Moreover, these changed bacteria were closely related to the diabetic-related serum indicators and proinflammatory cytokines. Conclusion These results suggest that FFSLD alleviates diabetic symptoms in T2DM rats through regulating GM composition and inhibiting inflammatory response, which clarify the therapeutic mechanism of FFSLD on T2DM and provide a theoretical basis for its further clinical application.
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Chow E, Yang A, Chung CHL, Chan JCN. A Clinical Perspective of the Multifaceted Mechanism of Metformin in Diabetes, Infections, Cognitive Dysfunction, and Cancer. Pharmaceuticals (Basel) 2022; 15:ph15040442. [PMID: 35455439 PMCID: PMC9030054 DOI: 10.3390/ph15040442] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 03/30/2022] [Accepted: 03/30/2022] [Indexed: 12/16/2022] Open
Abstract
In type 2 diabetes, ecological and lifecourse factors may interact with the host microbiota to influence expression of his/her genomes causing perturbation of interconnecting biological pathways with diverse clinical course. Metformin is a plant-based or plant-derived medicinal product used for the treatment of type 2 diabetes for over 60 years and is an essential drug listed by the World Health Organization. By reducing mitochondrial oxidative phosphorylation and adenosine triphosphate (ATP) production, metformin increased AMP (adenosine monophosphate)-activated protein kinase (AMPK) activity and altered cellular redox state with reduced glucagon activity, endogenous glucose production, lipogenesis, and protein synthesis. Metformin modulated immune response by directly reducing neutrophil to lymphocyte ratio and improving the phagocytic function of immune cells. By increasing the relative abundance of mucin-producing and short-chain-fatty-acid-producing gut microbes, metformin further improved the host inflammatory and metabolic milieu. Experimentally, metformin promoted apoptosis and reduced proliferation of cancer cells by reducing their oxygen consumption and modulating the microenvironment. Both clinical and mechanistic studies support the pluripotent effects of metformin on reducing cardiovascular–renal events, infection, cancer, cognitive dysfunction, and all-cause death in type 2 diabetes, making this low-cost medication a fundamental therapy for individualization of other glucose-lowering drugs in type 2 diabetes. Further research into the effects of metformin on cognitive function, infection and cancer, especially in people without diabetes, will provide new insights into the therapeutic value of metformin in our pursuit of prevention and treatment of ageing-related as well as acute and chronic diseases beyond diabetes.
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Affiliation(s)
- Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China; (E.C.); (A.Y.); (C.H.L.C.)
- The Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China
- Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China; (E.C.); (A.Y.); (C.H.L.C.)
- The Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China
| | - Colin H. L. Chung
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China; (E.C.); (A.Y.); (C.H.L.C.)
| | - Juliana C. N. Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China; (E.C.); (A.Y.); (C.H.L.C.)
- The Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong 999077, China
- Correspondence: ; Tel.: +852-3505-3138
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12
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Bao S, Wang X, Cho SB, Wu YL, Wei C, Han S, Bao L, Wu Q, Ao W, Nan JX. Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells. Front Pharmacol 2021; 12:656220. [PMID: 34497509 PMCID: PMC8419282 DOI: 10.3389/fphar.2021.656220] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Accepted: 07/21/2021] [Indexed: 12/25/2022] Open
Abstract
We have previously reported that Agriophyllum oligosaccharides (AOS) significantly enhance glycemic control by increasing the activation of insulin receptor (INS-R), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), peroxisome proliferator-activated receptor (PPAR)-γ, and glucose transporter 4 (Glut4) proteins in hepatic tissues. However, the effect of glucose control by AOS on the regulation of pancreatic tissues in db/db mice and MIN6 cells remains to be determined. An oral dose of AOS (380 or 750 mg/kg) was administered to type-2 diabetic db/db mice for 8 weeks to determine whether AOS regulates glucose by the INS-R/IRS/Glut4-mediated insulin pathway. Meanwhile, the effects of AOS on glucose uptake and its related signaling pathway in MIN6 cells were also investigated. The results showed that the random blood glucose (RBG) level in the AOS-treated group was lower than that in the control group. AOS reduced the levels of glycated hemoglobin (HbA1c) and free fatty acid (FFA) and significantly improved the pathological changes in the pancreatic tissues in db/db mice. Moreover, immunohistochemical analysis revealed that the expression of INS-R, IRS-1, IRS-2, and Glut4 was increased in the AOS-treated group than in the model group. Further, in vitro experiments using MIN6 cells showed that AOS regulated INS-R, IRS-1, IRS-2, and Glut4 protein and mRNA levels and attenuated insulin resistance and cell apoptosis. The results of both in vitro and in vivo experiments were comparable. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometric analysis of AOS with precolumn derivatization with 3-amino-9-ethylcarbazole (AEC) tentatively identified five types of sugars: glucose, lactose, rutinose, glucuronic acid, and maltotriose. Our present study clearly showed that AOS is efficacious in preventing hyperglycemia, possibly by increasing insulin sensitivity and improving IR by regulating the INS-R/IRS/Glut4 insulin signal pathway. Therefore, AOS may be considered as a potential drug for diabetes treatment.
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Affiliation(s)
- Shuyin Bao
- Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China.,Medical College, Inner Mongolia University for Nationalities, Tongliao, China
| | - Xiuzhi Wang
- Department of Medicines and Foods, Tongliao Vocational College, Tongliao, China.,The Research Institute of Traditional Mongolian Medicine Engineering Technology, Tongliao, China
| | - Sung Bo Cho
- College of Traditional Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao, China
| | - Yan-Ling Wu
- Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China
| | - Chengxi Wei
- Medical College, Inner Mongolia University for Nationalities, Tongliao, China
| | - Shuying Han
- Basic Medical College, North China University of Science and Technology, Tangshan, China
| | - Liming Bao
- College of Traditional Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao, China
| | - Qiong Wu
- Department of Cardiology, Tongliao Second People's Hospital, Tongliao, China
| | - Wuliji Ao
- The Research Institute of Traditional Mongolian Medicine Engineering Technology, Tongliao, China.,College of Traditional Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao, China
| | - Ji-Xing Nan
- Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, China.,Clinical Research Center, Yanbian University Hospital, Yanji, China
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13
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Song A, Zhang C, Meng X. Mechanism and application of metformin in kidney diseases: An update. Biomed Pharmacother 2021; 138:111454. [PMID: 33714781 DOI: 10.1016/j.biopha.2021.111454] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Revised: 02/26/2021] [Accepted: 02/27/2021] [Indexed: 01/08/2023] Open
Abstract
Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes mellitus (T2DM), acting via indirect activation of 5' Adenosine monophosphate-activated Protein Kinase (AMPK). Beyond the anti-diabetic effect, accumulative pieces of evidence have revealed that metformin also everts a beneficial effect in diverse kidney diseases. In various acute kidney diseases (AKI) animal models, metformin protects renal tubular cells from inflammation, apoptosis, reactive oxygen stress (ROS), endoplasmic reticulum (ER) stress, epithelial-mesenchymal transition (EMT) via AMPK activation. In diabetic kidney disease (DKD), metformin also alleviates podocyte loss, mesangial cells apoptosis, and tubular cells senescence through AMPK-mediated signaling pathways. Besides, metformin inhibits cystic fibrosis transmembrane conductance regulator (CFTR)-mediated fluids secretion and the mammalian target of rapamycin (mTOR)-involved cyst formation negatively regulated by AMPK in autosomal dominant polycystic kidney disease (APDKD). Furthermore, metformin also contributes to the alleviation of urolithiasis and renal cell carcinoma (RCC). As the common pathway for chronic kidney disease (CKD) progressing towards end-stage renal disease (ESRD), renal fibrosis is ameliorated by metformin, to a great extent dependent on AMPK activation. However, clinical data are not always consistent with preclinical data, some clinical investigations showed the unmeaningful even detrimental effect of metformin on T2DM patients with kidney diseases. Most importantly, metformin-associated lactic acidosis (MALA) is a vital issue restricting the application of metformin. Thus, we conclude the application of metformin in kidney diseases and uncover the underlying molecular mechanisms in this review.
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Affiliation(s)
- Anni Song
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Chun Zhang
- Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Xianfang Meng
- Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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14
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Wu M, Xu H, Liu J, Tan X, Wan S, Guo M, Long Y, Xu Y. Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms. J Diabetes Res 2021; 2021:6673525. [PMID: 34007848 PMCID: PMC8102119 DOI: 10.1155/2021/6673525] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 04/01/2021] [Accepted: 04/05/2021] [Indexed: 12/16/2022] Open
Abstract
Fibrosis is a physiological response to organ injury and is characterized by the excessive deposition of connective tissue components in an organ, which results in the disruption of physiological architecture and organ remodeling, ultimately leading to organ failure and death. Fibrosis in the lung, kidney, and liver accounts for a substantial proportion of the global burden of disability and mortality. To date, there are no effective therapeutic strategies for controlling fibrosis. A class of metabolically targeted chemicals, such as adenosine monophosphate-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPAR) agonists, shows strong potential in fighting fibrosis. Metformin, which is a potent AMPK activator and is the only recommended first-line drug for the treatment of type 2 diabetes, has emerged as a promising method of fibrosis reduction or reversion. In this review, we first summarize the key experimental and clinical studies that have specifically investigated the effects of metformin on organ fibrosis. Then, we discuss the mechanisms involved in mediating the antifibrotic effects of metformin in depth.
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Affiliation(s)
- Maoyan Wu
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 646000
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, Sichuan, China 646000
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China 646000
| | - Huiwen Xu
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 646000
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, Sichuan, China 646000
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China 646000
| | - Jingyu Liu
- Southwest Medical University, Luzhou, Sichuan, China 646000
| | - Xiaozhen Tan
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, Sichuan, China 646000
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China 646000
| | - Shengrong Wan
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 646000
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, Sichuan, China 646000
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China 646000
| | - Man Guo
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, Sichuan, China 646000
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China 646000
| | - Yang Long
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 646000
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, Sichuan, China 646000
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China 646000
| | - Yong Xu
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 646000
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, Sichuan, China 646000
- Sichuan Clinical Research Center for Nephropathy, Luzhou, Sichuan, China 646000
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15
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Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:8708236. [PMID: 32104542 PMCID: PMC7035567 DOI: 10.1155/2020/8708236] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 11/07/2019] [Accepted: 01/23/2020] [Indexed: 01/13/2023]
Abstract
Senescence of renal tubular epithelial cells plays an important role in diabetic nephropathy, but the mechanism is unknown. Metformin may alleviate diabetic nephropathy by reducing this senescence. This study is aimed at clarifying the effects and mechanism of metformin on the senescence of renal tubular epithelial cells in diabetic nephropathy. We found that metformin reduced the expression of senescence-associated gene P21 in high-glucose-induced (30 mmol/L) renal tubular epithelial cells and decreased the β-galactosidase positive staining rate (decreased 16%, p < 0.01). Metformin was able to reduce senescence by upregulating the expression of RNA-binding protein MBNL1 and miR-130a-3p and reducing STAT3 expression. MBNL1 prolonged the half-life of miR-130a-3p, and miR-130a-3p could negatively regulate STAT3 by binding to its mRNA 3′UTR. In db/db diabetic mice, we found an enhanced senescence level combined with low expression of MBNL1 and miR-130a-3p and high expression of STAT3 compared with db/m control mice during nephropathy development. Meanwhile, metformin (200 mg/kg/day) could increase the expression of MBNL1 and miR-130a-3p and decreased STAT3 expression, thus reducing this senescence in db/db mice. Our results suggest that metformin reduces the senescence of renal tubular epithelial cells in diabetic nephropathy via the MBNL1/miR-130a-3p/STAT3 pathway, which provided new ideas for the therapy of this disease.
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16
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Shi Y, Chen R, Xie J, Li L, Liu G, Zheng M, Zhang N. Determination and Pharmacokinetics of Okanin in Rat Plasma by UltraHigh Performance Liquid Chromatography Coupled with Triple-Quadrupole Tandem Mass Spectrometry. JOURNAL OF ANALYTICAL METHODS IN CHEMISTRY 2020; 2020:4247128. [PMID: 32908778 PMCID: PMC7474779 DOI: 10.1155/2020/4247128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 06/08/2020] [Accepted: 08/04/2020] [Indexed: 05/06/2023]
Abstract
Okanin is a major flavonoid found in Coreopsis tinctoria Nutt., arousing huge interest recently for its considerable biological characteristics including antioxidant, antineurotoxic, and antidiabetic activities. An ultrahigh performance liquid chromatography triple-quadrupole tandem mass spectrometry (UPLC-MS) was successfully used to determine okanin in rat plasma after oral administration of okanin. Bavachalcone acted as an internal standard (IS). By gradient elution, IS and analyte were separated on a C18 column for 7 min at a flow rate of 0.25 mL/min with acetonitrile-0.1% acetic acid mobile phase. The stability, matrix effect, extraction recovery, accuracy, precision, linearity, and selectivity of the method were firstly demonstrated. The major pharmacokinetic parameters of okanin in rat plasma were then measured using the developed UPLC-MS method. An UPLC-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was finally established to obtain the specific and accurate mass of okanin in rat plasma after oral administration, and its proposed fragmentation was further elaborated.
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Affiliation(s)
- Yurui Shi
- The College of Chemistry, Changchun Normal University, Changchun 130032, China
| | - Rongda Chen
- The College of Chemistry, Changchun Normal University, Changchun 130032, China
| | - Jing Xie
- The College of Chemistry, Changchun Normal University, Changchun 130032, China
| | - Li Li
- The College of Chemistry, Changchun Normal University, Changchun 130032, China
| | - Guiming Liu
- The College of Chemistry, Changchun Normal University, Changchun 130032, China
| | - Meizhu Zheng
- The College of Chemistry, Changchun Normal University, Changchun 130032, China
| | - Ning Zhang
- The College of Jiamusi, Heilongjiang University of Chinese Medicine, Harbin 150040, China
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17
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Lv J, Wu Y, Mai Y, Bu S. Noncoding RNAs in Diabetic Nephropathy: Pathogenesis, Biomarkers, and Therapy. J Diabetes Res 2020; 2020:3960857. [PMID: 32656264 PMCID: PMC7327582 DOI: 10.1155/2020/3960857] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 04/27/2020] [Accepted: 05/20/2020] [Indexed: 12/14/2022] Open
Abstract
The correlation between diabetes and systematic well-being on human life has long established. As a common complication of diabetes, the prevalence of diabetic nephropathy (DN) has been increasing globally. DN is known to be a major cause of end-stage kidney disease (ESKD). Till now, the molecular mechanisms for DN have not been fully explored and the effective therapies are still lacking. Noncoding RNAs are a class of RNAs produced by genome transcription that cannot be translated into proteins. It has been documented that ncRNAs participate in the pathogenesis of DN by regulating inflammation, apoptosis, autophagy, cell proliferation, and other pathological processes. In this review, the pathological roles and diagnostic and therapeutic potential of three types of ncRNAs (microRNA, long noncoding RNA, and circular RNA) in the progression of DN are summarized and illustrated.
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Affiliation(s)
- Jiarong Lv
- Diabetes Research Center, Medical School of Ningbo University, Ningbo, 315000 Zhejiang, China
| | - Yu Wu
- Diabetes Research Center, Medical School of Ningbo University, Ningbo, 315000 Zhejiang, China
| | - Yifeng Mai
- The Affiliated Hospital of Medical School of Ningbo University, Ningbo, 315000 Zhejiang, China
| | - Shizhong Bu
- Diabetes Research Center, Medical School of Ningbo University, Ningbo, 315000 Zhejiang, China
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