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JunB contributes to the epithelial‐mesenchymal transition in response to TGF‐β (LB277)
Author(s) -
Gervasi Megan,
BianchiSmiraglia Anna,
Cummings Michael,
Bakin Andrei
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb277
Subject(s) - junb , epithelial–mesenchymal transition , snai1 , microbiology and biotechnology , cancer research , smad , transforming growth factor , transcription factor , biology , chemistry , downregulation and upregulation , gene , genetics
The process of epithelial‐mesenchymal transition (EMT) is important in tissue fibrosis, wound healing and cancer. Transforming growth factor beta (TGF‐β) induces EMT and fibrotic proteins in a variety of responsive cells via a mechanism that is not fully understood. This study identifies a critical role of JunB in the EMT and fibrotic process in response to TGF‐β. Knock‐down of the immediate‐early response gene JunB by siRNA abrogates TGF‐β‐induced disruption of epithelial cell junctions, formation of actin fibers, focal adhesions and expression of fibrotic proteins. JunB contributes to Smad‐mediated repression of Id2 helix‐loop‐helix protein but does not affect the induction of Hmga2, Snail and Slug. Knock‐down of JunB abolishes up‐regulation of ATF3, which is required for Id2 repression. Importantly, JunB contributes to the TGF‐β‐induced fibrotic response by regulating expression of fibronectin, fibulin‐2, tropomyosin (Tpm1) and β3‐integrin, which play critical roles in matrix deposition, cell‐matrix adhesion and actin stress‐fibers. In summary, JunB provides important input in setting the transcriptional program of the EMT and fibrotic responses to TGF‐β. Thus, JunB represents an important target in diseases associated with EMT, including cancer and fibrosis. Grant Funding Source : Supported by R01 CA95263