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

Objectives Metformin (MET) has protective effect on diabetic nephropathy (DN). This study aims to demystify the mechanism of MET function in DN. Methods 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-beta 1 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. Results 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-beta 1 expression by sponging miR-143-3p. Furthermore, MET inhibited extracellular matrix accumulation, inflammation and proliferation by regulating H19/miR-143-3p/TGF-beta 1 axis. Conclusions 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-beta 1 axis, which suggested that the H19/miR-143-3p/TGF-beta 1 axis could be a valuable target for DN therapies.