The Relationship between Time, Race, and Estrogen Receptor Alpha in Estradiol-Induced Dermal Fibrosis.

Autor: Baker Frost D; Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA., Savchenko A; Chobanian & Avedisian School of Medicine, Boston University, 72 E. Concord Street, Boston, MA 02118, USA., Feghali-Bostwick C; Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425, USA., Wolf B; Department of Public Health Sciences, Medical University of South Carolina, 135 Cannon Street, Room 305F, Charleston, SC 29425, USA.
Jazyk: angličtina
Zdroj: Biomedicines [Biomedicines] 2024 Jan 15; Vol. 12 (1). Date of Electronic Publication: 2024 Jan 15.
DOI: 10.3390/biomedicines12010182
Abstrakt: In the skin, estradiol (E2) promotes profibrotic and proinflammatory cytokines, contributing to extracellular matrix (ECM) deposition. However, the magnitude of the response differs. Using the human skin organ culture model, we evaluated donor characteristics and correlations that contribute to E2-induced interleukin-6 ( IL-6 ), transforming growth factor beta 1 and 2 ( TGFB1 and TGFB2 ), collagen IA2 ( Col IA2 ), collagen IIIA1 ( Col IIIA1 ), and fibronectin ( FN ) expressions. In vehicle- and E2-treated dermal skin tissue transcripts, we confirm differences in the magnitude; however, there were positive correlations between profibrotic mediators and ECM components 48 h after E2 treatment. Also, positive correlations exist between baseline and E2-induced TGFB1 , IL-6 , Col IIIA1 , and FN transcripts. Since estrogen receptor alpha (ERA) can propagate E2's signal, we measured and detected differences in its baseline and fold change transcript levels, with a significant decline in baseline levels 48 h after incubation and an increase 48 h after E2 treatment. There was a trend to higher transcript levels in African American donors 24 h earlier. Finally, E2-induced ERA transcript levels negatively correlated with its own baseline levels and positively correlated with FN , TGFB1 , and Col IA2 transcript levels. Therefore, our data suggest ERA, E2 exposure time, and race/ethnicity contribute to E2-induced dermal fibrosis.
Databáze: MEDLINE