Role of hypoxia inducible factor 1α-mediated signaling pathway in angiotensin Ⅱ-induced renal interstitial fibrosis
10.3760/cma.j.issn.1001-7097.2011.03.014
- VernacularTitle:缺氧诱导因子1α介导的信号通路在血管紧张素Ⅱ诱导肾间质纤维化中的作用
- Author:
Lin TANG
;
Qing GUO
;
Cuicui ZHANG
;
Zhangsuo LIU
;
Xiaoxue ZHANG
- Publication Type:Journal Article
- Keywords:
Angiotensin Ⅱ;
Fibrosis;
Hypoxia-inducible factor 1,alpha subunit;
Renal tubular epithelial cells;
Prolyl hydroxylase 2:Tissue inhibitor of metalloproteinase-1
- From:
Chinese Journal of Nephrology
2011;27(3):194-197
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of hypoxia inducible factor 1α(HIF-1α)-mediated signaling pathway in angiotensin Ⅱ(Ang Ⅱ)induced renal interstitial fibrosis. Methods Renal tubular epithelial cells were cultured and treated with different concentrations (10-9-10-6 mol/L)of Ang Ⅱ for 24 h and 48 h.Real-time quantitative PCR and Western blotting were preformed to detect the mRNA and protein expressions of HIF-1α,prolyl hydroxylase 2 (PHD2)and tissue inhibitor of metalloproteinase 1 (TIMP-1)in renal tubular epithelial cells. Results HIF-1αmRNA level was increased with Ang Ⅱ treatment in a concentration dependent manner.When cells were treated with Ang Ⅱ concentration at 10-7mol/L for 24 h,the mRNA level was markedly increased by 166%.Furthermore,by real-time quantitative PCR and Western blotting,compared with the control group,Ang Ⅱincreased the mRNA and protein levels of HIF-1α and TIMP-1 (P<0.05,respectively),while the mRNA and protein levels of PHD2 were decreased markedly (P<0.05,respectively)in renal tubular epithelial cells.Conclusion Ang Ⅱ reduces HIF-1αdegradation in renal tubular epithelial cells probably by reducing the expression of PHD2,which increases the expressions of HIF-1α and TIMP-1 involved in renal interstitial fibrosis.
