Metformin Inhibits Advanced Glycation End Products-Induced Cell Apoptosis and Oxidative Stress of Human Skin Fibroblasts by Downregulating MicroRNA-126

To determine the influence of metformin on the proliferation and apoptosis of advanced glycation end products-induced primary skin fibroblasts and its mechanism. Human skin fibroblasts were purchased and treated with advanced glycation end products of different concentrations separately, on which the fibroblasts were intervened by metformin of different concentrations. The proliferation and apoptosis of cells treated with advanced glycation end products and metformin were evaluated and the changes of oxidative stress markers and microRNA-126 in the cells were also determined. In addition, the cells treated with metformin were transfected with miR-126 mimics and blank plasmids and microRNA-126 mimics, separately, to explore whether the transfection can weaken the effects of metformin. Human skin fibroblasts lines HSF2 showed a decrease in proliferation and superoxide dismutase and an increase in apoptosis rate, reactive oxygen species and malondialdehyde after being treated with advanced glycation end products and metformin weakened the influence of advanced glycation end products on proliferation, apoptosis as well as oxidative stress of human skin fibroblasts cells. In addition, HSF2 cells showed increased microRNA-126 expression after being treated with advanced glycation end products and metformin could inhibit this increase. Transfection of microRNA-126 mimics weakened the protective effect of metformin on HSF2 cells treated with advanced glycation end products. Metformin can inhibit advanced glycation end products-induced cell apoptosis and oxidative stress of human skin fibroblasts by downregulating microRNA-126.