RTEF-1 protects against oxidative damage induced by H2O2 in human umbilical vein endothelial cells through Klotho activation.

Abstract

Oxidative stress is a main risk factor of vascular aging, which may lead to age-associated diseases. Related transcriptional enhancer factor-1 (RTEF-1) has been suggested to regulate many genes expression which are involved in the endothelial angiogenesis and vasodilation. However, whether RTEF-1 has a direct role in anti-oxidation and what specific genes are involved in RTEF-1-driven anti-oxidation have not been elucidated. In this study, we found that overexpressing RTEF-1 in H2O2-treated human umbilical vein endothelial cells decreased senescence-associated-β-galactosidase (SA-β-gal)-positive cells and G0/G1 cells population. The expressions of p53 and p21 were decreased in H2O2-treated RTEF-1 o/e human umbilical vein endothelial cells. However, specific small interfering RNA of RTEF-1 totally reversed the anti-oxidation effect of RTEF-1 and inhibited RTEF-1-induced decreased p53 and p21 expressions. It demonstrated that RTEF-1 could protect cells from H2O2-induced oxidative damage. In addition, we demonstrated that RTEF-1 could up-regulate Klotho gene expression and activate its promoter. Furthermore, Klotho small interfering RNA significantly blocked RTEF-1-driven endothelial cell protection from H2O2-induced oxidative damage and increased p53 and p21 expressions. These results reveal that RTEF-1 is a potential anti-oxidation gene and can prevent H2O2-induced endothelial cell oxidative damage by activating Klotho.