Metformin inhibits extracellular matrix accumulation, inflammation and proliferation of mesangial cells in diabetic nephropathy by regulating H19/miR-143-3p/TGF-β1 axis

• Published in: Journal of pharmacy and pharmacology Vol. 72; no. 8; p. 1101
• Main Authors: Xu, Jiang, Xiang, Ping, Liu, Linqing, Sun, Jianran, Ye, Shandong
• Format: Journal Article
• Language: English
• Published: England 01.08.2020
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Cell Line; Cell Proliferation - drug effects; Diabetic Nephropathies - genetics; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic Nephropathies - prevention & control; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Gene Expression Regulation; Hypoglycemic Agents - pharmacology; Inflammation Mediators - metabolism; Mesangial Cells - drug effects; Mesangial Cells - metabolism; Mesangial Cells - pathology; Metformin - pharmacology; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; miR-143-3p; H19; TGF-β1; metformin; diabetic nephropathy
• DOI: 10.1111/jphp.13280

Metformin (MET) has protective effect on diabetic nephropathy (DN). This study aims to demystify the mechanism of MET function in DN. Mouse glomerular membrane epithelial cell line SV40-MES-13 was treated with normal or high glucose combined with or without MET. The relationships among H19, miR-143-3p and TGF-β1 were evaluated by luciferase reporter assay. MTT assay was performed to detect cell proliferation. The levels of inflammatory factors were investigated by enzyme-linked immunosorbent assay. Quantitative real-time PCR and western blot were performed to examine gene and protein expression. H19 was up-regulated in the SV40-MES-13 cells after treated with high glucose, which was effectively repressed by MET treatment. MET promoted extracellular matrix accumulation, inflammation and proliferation in the SV40-MES-13 cells after treated with high glucose. These influences conferred by MET were abolished by H19 overexpression. H19 regulated TGF-β1 expression by sponging miR-143-3p. Furthermore, MET inhibited extracellular matrix accumulation, inflammation and proliferation by regulating H19/miR-143-3p/TGF-β1 axis. Our studies demonstrated that the protective effect of MET on DN was attributed to the inhibition of proliferation, inflammation and ECM accumulation in mesangial cells via H19/miR-143-3p/TGF-β1 axis, which suggested that the H19/miR-143-3p/TGF-β1 axis could be a valuable target for DN therapies.