RTEF-1 protects against oxidative damage induced by H2O2 in human umbilical vein endothelial cells through Klotho activation
RTEF-1 protects against oxidative damage induced by H2O2 in human umbilical vein endothelial cells through Klotho activation
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DOI：
10.1177/1535370215587914
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发表时间：
2015-12
影响因子：
3.2
通讯作者：
Shan Sun;Bei Cheng;P. Sun;Xiaohua Wu;Qinqin Wu;P. He
中科院分区：
文献类型：
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作者：
Shan Sun;Bei Cheng;P. Sun;Xiaohua Wu;Qinqin Wu;P. He
氧化应激是血管老化的主要危险因素，可能导致与年龄相关的疾病。相关转录增强因子-1 （RTEF-1）被认为调控许多参与内皮血管生成和血管舒张的基因表达。然而，RTEF-1是否在抗氧化中起直接作用，以及哪些特定基因参与了RTEF-1驱动的抗氧化，目前还不清楚。在本研究中，我们发现在h2o2处理的人脐静脉内皮细胞中过表达RTEF-1可减少衰老相关-β-半乳糖苷酶（SA-β-gal）阳性细胞和G0/G1细胞群。在h2o2处理的RTEF-1 o/e人脐静脉内皮细胞中，p53和p21的表达降低。然而，RTEF-1的特异性小干扰RNA完全逆转了RTEF-1的抗氧化作用，抑制了RTEF-1诱导的p53和p21表达的下降。结果表明，RTEF-1对h2o2诱导的细胞氧化损伤具有保护作用。此外，我们证明RTEF-1可以上调Klotho基因的表达并激活其启动子。此外，Klotho小干扰RNA显著阻断rtef -1驱动的内皮细胞对h2o2诱导的氧化损伤的保护，并增加p53和p21的表达。这些结果表明RTEF-1是一个潜在的抗氧化基因，可以通过激活Klotho来预防h2o2诱导的内皮细胞氧化损伤。
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.