17ß-Estradiol inhibits hydrogen peroxide-induced senescence and apoptosis in human umbilical vein endothelial cells by regulating the THBS1/TGF-ß/Smad axis.
Mol Cell Endocrinol
; 580: 112111, 2024 Jan 15.
Article
in En
| MEDLINE
| ID: mdl-37979907
ABSTRACT
Before menopause, females exhibit a lower incidence of cardiovascular disease than age-matched males, possibly owing to the protective effects of sex hormones. 17ß-estradiol (17ß-E2) protects against oxidative stress-induced injury by suppressing thrombospondin-1 (THBS1) expression in endothelial cells. Here, we examined the role of 17ß-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-ß kinase inhibitor) treatments were applied. THBS1 knockdown repressed, and its overexpression aggravated, H2O2-induced cell injury, affecting cell death, proliferation, senescence, and apoptosis. 17ß-E2 inhibited THBS1 mRNA and protein expression time- and dose-dependently, by targeting ERß. THBS1 overexpression blocked 17ß-E2 from preventing H2O2-induced injury, significantly activating the TGF-ß/Smad pathway. 17ß-E2 inhibited H2O2-induced oxidative stress by downregulating THBS1 expression and TGF-ß/Smad signaling in HUVECs. The THBS1/TGF-ß/Smad axis could thus be a therapeutic target.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transforming Growth Factor beta
/
Hydrogen Peroxide
Limits:
Female
/
Humans
Language:
En
Journal:
Mol Cell Endocrinol
Year:
2024
Document type:
Article