Rosiglitazone Inhibited Aldosterone-Induced Mesangial Cell Proliferation via Blocking Phosphatidyl Inositol 3-Kinase Activation
- VernacularTitle:罗格列酮通过阻断磷酸肌醇-3激酶抑制醛固酮诱导的肾小球系膜细胞增殖的作用
- Author:
kang-kang, XU
;
ai-hua, ZHANG
;
gui-xia, DING
- Publication Type:Journal Article
- Keywords:
aldosterone;
mesangial cell;
peroxisome proliferator-activated receptor-?;
rosiglitazone
- From:Journal of Applied Clinical Pediatrics
2006;0(17):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the inhibitory effect of rosiglitazone of peroxisome proliferator-activated receptor-?(PPAR?) agonist on aldosterone-induced mesangial cell(MC) proliferation.Methods Mouse primary MC were cultured and treated with aldosterone(100 nmol/L) in the presence or absence of rosiglitazone(1.0,2.5,5.0,10.0 ?mol/L).The incorporation of 3H-thymidine(3H-TdR) and cell count were used as the measure of MC proliferation.Cyclin D1 and cyclin A expression,PI3K and Akt phosphorylation were determined by Western blot analysis.Results 1.Aldosterone induced MC proliferation,as assessed by 3H-TdR incorporation and cell number,which were increased by 2.46-and 2.14-fold,respectively,in aldosterone-treated cells.Aldosterone-induced MC proliferation was inhibited by PPAR? agonist rosiglitazone in dose-dependent manner in mouse MC.2.Aldosterone induced cyclin D1 and cyclin A expression.Rosiglitazone reduced aldosterone-induced cyclin D1 and cyclin A expression in dose-dependent manner.3.Aldosterone induced PI3K/Akt activation in dose-dependent manner,incubation with 100 nmol/L aldosterone for 60 min,phosphorylation PI3K and Akt expression increased by above 3.0-fold.4.PI3K inhibitor LY294002 and Akt inhibitor significantly inhibited aldosterone-induced cyclin D1 and cyclin A expression.5.Rosiglitazone significantly inhibited aldosterone-induced PI3K/Akt activation,10 ?mol/L rosiglitazone almost completely blocked aldosterone-induced PI3K/Akt activation.Conclusion Rosiglitazone can block aldosterone-induced MC proliferation via inhibition of PI3K/Akt activation.
