Mir-217 promotes inflammation and fibrosis induced by high glucose in rat glomerular mesangial cells via Sirt1/HIF-1α signal pathway

Abstract

Objective To explore the roles of MircroRNA-217(Mir-217), silent information regulator 1(Sirt1), and hypoxia-inducible factor-1 α(HIF-1α)in high glucose-induced inflammation and fibrosis in rat glomerular mesangial cells(RMCs). Methods RMCs were pre-incubated with a Sirt1 activator resveratrol prior to high glucose treatment or transfected with Sirt1 small interfering RNA(siRNA), HIF-1α siRNA, and Mir-217 inhibitor. Real-time PCR was used to analyze the expressions of Mir-217, Sirt1 mRNA, and HIF-1α mRNA; Western blot was used to observe the protein expressions of Sirt1, HIF-1α, connective tissue growth factor(CTGF), endothelin-1(ET-1), and fibronectin(FN). Enzyme-linked immunosorbent assay was applied to detect protein expression of transforming growth factor-β1(TGF-β1)and vascular endothelial growth factor(VEGF). Results High glucose increased Mir-217, HIF-1α, CTGF, ET-1, FN, TGF-β1, and VEGF expressions(all P<0.01), while decreased Sirt1 expression. In addition, Mir-217 gene silencing or 25 μmol/L resveratrol suppressed high glucose-stimulated expressions of HIF-1α, CTGF, endothelin-1, FN, TGF-β1, and VEGF(all P<0.01). Conclusion Mir-217 mediates high glucose-induced inflammation and fibrosis in RMCs via Sirt1/HIF-1α signal pathway. This study provides new evidence to clarify the protective mechanisms of Sirt1 in diabetic nephropathy. (Chin J Endocrinol Metab, 2016, 32: 556-563) Key words: MicroRNA; MicroRNA-217; Silent information regulator 1; Hypoxia-inducible factor-1α; Diabetic nephropathy