Peroxisome proliferator-activated receptor-γ agonist inhibited aldosterone-induced mesangial cell proliferation

Objective:To investigate the role of oxidative stress in aldosterone(ALDO)-induced mesangial cell(MC)proliferation, and to detect the inhibitory effect of peroxisome prnliferator-activated receptor-y(PPARγ)agonist on ALDO-induced MC proliferation. Methods:Mouse primary mesangial cells were treated with ALDO(100 nmol/L)in the presence or absence of N-acytosistin(NAC, 10μmol/L)or Rosiglitazone(1.0,2.3,5.0,10.0μmol/L).MC proliferation was measured by ~3H-thymidine incoporation.MC cell-cycle was analyzed by flow cytometry.Cyclin D1 and cyclin A expression was determined by Western blot analysis.Reactive oxygen species (ROS)production was measured by 2',7'-dichlorofluorescein diacetate(DCFDA)fluorescence.Results:①ALDO-induced MC prolif- eration was inhibited by PPARγagonist rosiglitazone in dose-dependent manner in mouse mesangial cells;②ALDO increased cell number in S-and G_2/M phase,which was inhibited by rosiglitazone;③Rosiglitazone reduced ALDO-induced eyelin D1 and cyclin A expression in dose-dependent manner;④NAC significantly inhibited ALDO-induced MC proliferation.Rosiglitazone dose-dependently inhibited ALDO-induced ROS production.Conclusions:ROS involved in ALDO-induced MC proliferation.PPARγligand rosiglitazone blocked ALDO-induced MC proliferation via inhibition of ROS production.