Role of extracellular signal-regulated kinases in aldosterone-induced rat mesangial cells proliferation
10.3760/cma.j.issn.1001-7097.2011.07.014
- VernacularTitle:细胞外信号调节蛋白激酶介导醛固酮诱导的肾小球系膜细胞增殖
- Author:
Li YAO
;
Li SUN
;
Min WEI
;
Danmei GE
;
Lining WANG
- Publication Type:Journal Article
- Keywords:
Extracellular signal-regulated MAP kinases;
Aldosterone;
Cell proliferation;
Mesangial cells
- From:
Chinese Journal of Nephrology
2011;27(7):520-524
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the role of extracellular signal-regulated kinases (ERK1/2) in aldosterone-induced rat mesangial cells (RMCs) proliferation. Methods RMCs were obtained from intact glomeruli of 4- to 6-week-old Sprague-Dawley rats and characterized according to published methods. RMCs between passages 5 and passages 10 were used. Protein levels of mineralocorticoid receptor (MR) in RMCs were analyzed by Western blotting. The cells were divided into the following groups: control group, PD98059 (10 (μmol/L) group, eplerenone (1 μmol/L) group, aldosterone (100 nmol/L) group, aldosterone (100 nmol/L) +PD98059 (10 μmol/L) group, aldosterone (100 nmol/L)+eplerenone (1 μmol/L) group. ERK1/2 activity was measured by Western blotting. Cell proliferation of RMCs was evaluated by [3H]-thymidine uptake measurements.Results MR protein expression in RMCs was confirmed by Western blotting. Aldosterone activated ERK1/2, and the maximal ERK1/2 activation induced by aldosterone was at a concentration of 100 nmol/L. Aldosterone (100 nmol/L)-induced activation of ERK1/2 peaked at 10 minutes (P＜0.05).Pretreatment with a selective MR antagonist eplerenone (1 μmol/L) significantly attenuated aldosterone-induced ERK1/2 phosphorylation. Aldosterone (100 nmol/L) treatment for 30 hours increased [3H]-thymidine incorporation of RMCs (135% ±8% of controls, P ＜0.05). Cellular proliferation induced by aldosterone could be prevented by pretreatment with eplerenone or an ERK (MEK) inhibitor PD988059. Conclusion Aldosterone induces RMCs proliferation through MR and ERK1/2 activation, which may contribute to the pathogenesis of glomerular mesangial injury.
