SMAD公司
脐静脉
氧化应激
细胞凋亡
细胞生物学
衰老
基因敲除
癌症研究
转化生长因子
生物
内分泌学
化学
内科学
医学
生物化学
体外
作者
Yifei Lv,Yizhou Huang,Huishou Fan,Yun-Xiu Zhao,Linjuan Ma,Yibing Lan,Chunming Li,Peiqiong Chen,Zheng Lou,Jianhong Zhou
标识
DOI:10.1016/j.mce.2023.112111
摘要
Before menopause, females exhibit a lower incidence of cardiovascular disease than age-matched males, possibly owing to the protective effects of sex hormones. 17β-estradiol (17β-E2) protects against oxidative stress-induced injury by suppressing thrombospondin-1 (THBS1) expression in endothelial cells. Here, we examined the role of 17β-E2-mediated THBS1 suppression in preventing cell senescence and apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultivated and treated with siRNA or overexpression plasmids to regulate THBS1. H2O2, estrogen-activity modulating drugs, and LY2109761 (a TGF-β kinase inhibitor) treatments were applied. THBS1 knockdown repressed, and its overexpression aggravated, H2O2-induced cell injury, affecting cell death, proliferation, senescence, and apoptosis. 17β-E2 inhibited THBS1 mRNA and protein expression time- and dose-dependently, by targeting ERβ. THBS1 overexpression blocked 17β-E2 from preventing H2O2-induced injury, significantly activating the TGF-β/Smad pathway. 17β-E2 inhibited H2O2-induced oxidative stress by downregulating THBS1 expression and TGF-β/Smad signaling in HUVECs. The THBS1/TGF-β/Smad axis could thus be a therapeutic target.
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