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Fli1 is a negative regulator of estrogen receptor ? in dermal fibroblasts.


ABSTRACT: Estrogen is an important regulator of dermal fibroblast functions, including extracellular matrix (ECM) synthesis. Estrogen mediates its effects through estrogen receptors (ERs), ER? and ER?; 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 ER?. We show that treatment of human dermal fibroblasts with transforming growth factor-? (TGF-?) increases ER? protein and mRNA levels. Similarly, ER? expression was increased in response to small interfering RNA (siRNA)-mediated depletion of Fli1, suggesting that Fli1 is a mediator of the TGF-? effects on ER? expression. Accordingly, we showed that Fli1 binds to the most proximal region of the ER? promoter, and dissociates from the promoter upon TGF-? treatment. An inverse correlation between Fli1 and ER? 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 ER? gene in dermal fibroblasts.

SUBMITTER: Hattori T 

PROVIDER: S-EPMC3825457 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Fli1 is a negative regulator of estrogen receptor α in dermal fibroblasts.

Hattori Tomoyasu T   Stawski Lukasz L   Nakerakanti Sashidhar S SS   Trojanowska Maria M  

The Journal of investigative dermatology 20110331 7


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 possibl  ...[more]

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