ABSTRACT
Objective To explore the effect and associated mechanism of fluvastatin combined with losartan on the expression of vascular endothelial growth factor (VEGF) in human podocytes induced by angiotensin (Ang)Ⅱ.Methods The differentiated human podocytes were cultured with various concentrations of Ang Ⅱ (10-9 to 10-5 mol/L) in vitro,followed by treatment of fluvastatin (10-7,10-6 and 10-5 mol/L),losartan (10-7,10-6 and 10-5 mol/L),extracellular signal-regulated kinase (ERK) inhibitor PD98059,and combination of fluvastatin and lolsartan.Expressions of VEGF and phosphorylation (p)ERK1/2 protein in podocytes were detected by Western blotting.RT-PCR was used to examine VEGF mRNA expression (P＜0.01).Results Ang Ⅱ up-regulated the expressions of VEGF and p-ERK1/2 in time-and dose-dependent manner.Above elevated expressions of VEGF and p-ERK1/2 induced by Ang Ⅱ could be down-regulated by fluvastatin,losartan and PD98059 respectively (P＜0.05).More obvious reduction of above expressions was found in combination of fluvastatin and losartan as compared to single agent (P ＜0.05).Conclusions Either fluvastatin or losartan can down-regulate the over-expression of VEGF and p-ERK1/2 induced by Ang Ⅱ in human podocytes,and their combination has a cooperative effect.The ERK signaling pathway may be one of the mechanisms of their renal protective effects.