title: Fli1 is a negative regulator of estrogen receptor α 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), 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.
authors: Arthritis Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors: Tomoyasu
authors: T
authors: Hattori
authors: Lukasz
authors: L
authors: Stawski
authors: Sashidhar S
authors: SS
authors: Nakerakanti
authors: Maria
authors: M
authors: Trojanowska
mesh_terms: D002478:Cells, Cultured; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D051789:Proto-Oncogene Protein c-fli-1 / Q000502:physiology*; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C078433:FLI1 protein, human; D051789:Proto-Oncogene Protein c-fli-1; D016212:Transforming Growth Factor beta