Mir-217 promotes inflammation and fibrosis induced by high glucose in rat glomerular mesangial cells via Sirt1/HIF-1αsignal pathway
10.3760/cma.j.issn.1000-6699.2016.07.007
- VernacularTitle:Mir-217通过 Sirt1/HIF-1α信号通路介导高糖诱导的大鼠肾小球系膜细胞炎症反应及纤维化
- Author:
Ying SHAO
;
Chuan LYU
;
Can WU
;
Yuehong ZHOU
;
Qiuyue WANG
- Publication Type:Journal Article
- Keywords:
MicroRNA;
MicroRNA-217;
Silent information regulator 1;
Hypoxia-inducible factor-1α;
Diabetic nephropathy
- From:Chinese Journal of Endocrinology and Metabolism
2016;32(7):556-563
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the roles of MircroRNA-217 ( Mir-217 ) , silent information regulator 1 (Sirt1), and hypoxia-inducible factor-1α(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-1αsiRNA, 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 25μmol/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-1αsignal pathway. This study provides new evidence to clarify the protective mechanisms of Sirt1 in diabetic nephropathy.
