First Author | Hattori T | Year | 2011 |
Journal | J Invest Dermatol | Volume | 131 |
Issue | 7 | Pages | 1469-76 |
PubMed ID | 21451544 | Mgi Jnum | J:180917 |
Mgi Id | MGI:5308165 | Doi | 10.1038/jid.2011.63 |
Citation | Hattori T, et al. (2011) Fli1 is a negative regulator of estrogen receptor alpha in dermal fibroblasts. J Invest Dermatol 131(7):1469-76 |
abstractText | Estrogen is an important regulator of dermal fibroblast functions, including extracellular matrix (ECM) synthesis. Estrogen mediates its effects through estrogen receptors (ERs), ERalpha and ERbeta; 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 ERalpha. We show that treatment of human dermal fibroblasts with transforming growth factor-beta (TGF-beta) increases ERalpha protein and mRNA levels. Similarly, ERalpha expression was increased in response to small interfering RNA (siRNA)-mediated depletion of Fli1, suggesting that Fli1 is a mediator of the TGF-beta effects on ERalpha expression. Accordingly, we showed that Fli1 binds to the most proximal region of the ERalpha promoter, and dissociates from the promoter upon TGF-beta treatment. An inverse correlation between Fli1 and ERalpha 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 ERalpha gene in dermal fibroblasts. |