JunB contributes to Id2 repression and the epithelial-mesenchymal transition in response to transforming growth factor-β

The process of epithelial mesenchymal transition (EMT) in response to transforming growth factor-beta (TGF-beta) contributes to tissue fibrosis, wound healing, and cancer via a mechanism that is not fully understood. This study identifies a critical role of JunB in the EMT and profibrotic responses to TGF-beta. Depletion of JunB by small interfering ribonucleic acid abrogates TGF-beta induced disruption of cell cell junctions, formation of actin fibers, focal adhesions, and expression of fibrotic proteins. JunB contributes to Smad-mediated repression of inhibitor of differentiation 2 through interaction with transcription repressor activating transcription factor 3. Importantly, JunB mediates the TGF-beta induction of pro-fibrotic response factors, fibronectin, fibulin-2, tropomyosin (Tpm 1), and integrin-beta 3, 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 profibrotic responses to TGF-beta. Thus, JunB represents an important target in diseases associated with EMT, including cancer and fibrosis.