The Effects And Mechanisms Of Fluvastatin On The Expression Of Vascular Endothelial Growth Factor (VEGF) In Human Podocytes Induced By High Glucose

Objective: To explore the effects and mechanisms of fluvastatin on the expression of vascular endothelial growth factor (VEGF) in podocytes induced by high glucose (HG).Methods: The normal immortalized human podocytes were cultured at 33℃and allowed to differentiate at 37℃for 14 days. The differentiated podocytes were incubated with medium (1%FBS and 5.5mmol/L D-glucose) for 24h to synchronize cell growth. Podocytes were randomly divided into several groups as follows: (1) high glucose (HG, 30mmol/L D-glucose) group: high glucose treated for 0, 6, 12 and 24h; (2) normal glucose (NG, 5.5mmol/L D-glucose) group, high glucose group, high glucose plus different concentrations (10-7,10-6 and 10-5mol/L) of fluvastatin or extracellular signal-regulated kinase (ERK) inhibitor PD98059 group, each group was incubated for 24h. The expressions of VEGF and pERK1/2 were detected by Western blot. The concentrations of angiotensinⅡin culture supernatant secreted by the podocytes were determined by radioimmunoassay.Results: 1. Compared with 0h group, high glucose increased the expressions of VEGF and pERK1/2 in podocytes in a time-dependent manner (P<0.05 or P<0.01).2. After 24h of exposure to HG, the levels of VEGF and pERK1/2 were increased markedly compared with NG group (P<0.05 or P<0.01). PD98059 inhibited the expression of VEGF and the phosphorylation of ERK1/2 indued by high glucose (P<0.01), and also fluvastatin abolished high glucose-induced VEGF expression and ERK1/2 phosphorylation in a dose-dependent manner (P<0.05 or P<0.01).3. After high glucose treated, the angiotensinⅡlevels were increased in a time-dependent manner in podocytes and reached the peak at 24h, but the differences were not significant (P>0.05); The podocytes secreted a level of angiotensinⅡin NG group after 24h, and the levels of angiotensinⅡwere higher in HG group than in NG group and lower in HG plus different concentrations (10-7, 10-6 and 10-5mol/L) of fluvastatin group than in HG group, but the differences were also not significant (P>0.05).Conclusion: The human podocytes product basic VEGF, pERK1/2 and angiotensinⅡin normal culture media. High glucose in culture media increases expressions of VEGF and pERK1/2 significantly in podocytes. Fluvastatin can markedly decrease VEGF and pERK1/2 expressions induced by high glucose, but the reductions of angiotensinⅡare not significant. These findings suggest that the renal protective effect of fluvastatin is partly related to its inhibition of the ERK signaling pathway to decrease the expression of VEGF, not through inhibition of angiotensinⅡexpression in diabetic kidney disease.