The following is a summary of “17β-Estradiol inhibits hydrogen peroxide-induced senescence and apoptosis in human umbilical vein endothelial cells by regulating the THBS1/TGF-β/Smad axis,” published in the December 2023 issue of Endocrinology by Lv, et al.
The preventive effects of sex hormones may be responsible for the reduced incidence of cardiovascular disease that is seen in females before menopause compared to an age-matched male population. Through its ability to decrease the production of thrombospondin-1 (THBS1) in endothelial cells, 17β-estradiol (17β-E2) protects against harm caused by oxidative stress exposure. For a study, researchers sought to investigate the function that 17β-E2-mediated THBS1 inhibition plays in avoiding the occurrence of cell senescence and apoptosis. To regulate THBS1, human umbilical vein endothelial cells (HUVECs) were grown and then treated with siRNA or plasmids that overexpressed the gene.
Therapeutic interventions included the administration of H2O2, estrogen-activity modifying medications, and LY2109761, which is a TGF-β kinase inhibitor. Cell death, proliferation, senescence, and apoptosis were all affected by H2O2-induced cell damage, which was suppressed by THBS1 knockdown and exacerbated by its overexpression. By targeting ERβ, 17β-E2 was able to decrease the production of THBS1 mRNA and protein in a manner that was both time- and dose-dependent.
The activation of the TGF-β/Smad pathway was considerably facilitated by the overexpression of THBS1, which prevented 17β-E2 from preventing damage caused by H2O2. Through the downregulation of THBS1 expression and TGF-β/Smad signaling in HUVECs, 17β-E2 was able to reduce the levels of oxidative stress that H2O2 caused. Therefore, the THBS1/TGF-β/Smad axis has the potential to serve as a therapeutic target.
Source: sciencedirect.com/science/article/abs/pii/S0303720723002629
