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Fli1 Is a Negative Regulator of Estrogen Receptor α in Dermal Fibroblasts.

Authors :
Hattori, Tomoyasu
Stawski, Lukasz
Nakerakanti, Sashidhar S.
Trojanowska, Maria
Source :
Journal of Investigative Dermatology. Jul2011, Vol. 131 Issue 7, p1469-1476. 8p.
Publication Year :
2011

Abstract

Estrogen is an important regulator of dermal fibroblast functions, including extracellular matrix (ECM) synthesis. Estrogen mediates its effects through estrogen receptors (ERs), ERα and ERβ; however, regulation of ERs in dermal fibroblasts remains poorly understood. Friend leukemia integration factor 1 (Fli1), a member of the Ets transcription factor family, has been shown to play a pivotal role in regulation of the ECM genes in dermal fibroblasts. The aim of this study was to examine a possible interaction between Fli1 and estrogen pathways, focusing on ERα. We show that treatment of human dermal fibroblasts with transforming growth factor-β (TGF-β) increases ERα protein and mRNA levels. Similarly, ERα expression was increased in response to small interfering RNA (siRNA)-mediated depletion of Fli1, suggesting that Fli1 is a mediator of the TGF-β effects on ERα expression. Accordingly, we showed that Fli1 binds to the most proximal region of the ERα promoter, and dissociates from the promoter upon TGF-β treatment. An inverse correlation between Fli1 and ERα expression levels was confirmed in cultured skin fibroblasts obtained from Fli1+/- mice and in the skin of Fli1+/- mice in vivo. This study supports a role of Fli1 as a negative regulator of the ERα gene in dermal fibroblasts. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0022202X
Volume :
131
Issue :
7
Database :
Academic Search Index
Journal :
Journal of Investigative Dermatology
Publication Type :
Academic Journal
Accession number :
61249153
Full Text :
https://doi.org/10.1038/jid.2011.63