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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2016 (archival)     Display Documents



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ID: 732365.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2016 (archival)
Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation.
Authors:Carthy, Jon M; Stöter, Martin; Bellomo, Claudia; Vanlandewijck, Michael; Heldin, Angelos; Morén, Anita; Kardassis, Dimitris; Gahman, Timothy C; Shiau, Andrew K; Bickle, Marc; Zerial, Marino; Heldin, Carl-Henrik; Moustakas, Aristidis
Date of Publication (YYYY-MM-DD):2016
Title of Journal:Scientific Reports
Volume:6
Sequence Number of Article:29868
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Plasticity in epithelial tissues relates to processes of embryonic development, tissue fibrosis and cancer progression. Pharmacological modulation of epithelial transitions during disease progression may thus be clinically useful. Using human keratinocytes and a robotic high-content imaging platform, we screened for chemical compounds that reverse transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition. In addition to TGF-β receptor kinase inhibitors, we identified small molecule epithelial plasticity modulators including a naturally occurring hydroxysterol agonist of the liver X receptors (LXRs), members of the nuclear receptor transcription factor family. Endogenous and synthetic LXR agonists tested in diverse cell models blocked α-smooth muscle actin expression, myofibroblast differentiation and function. Agonist-dependent LXR activity or LXR overexpression in the absence of ligand counteracted TGF-β-mediated myofibroblast terminal differentiation and collagen contraction. The protective effect of LXR agonists against TGF-β-induced pro-fibrotic activity raises the possibility that anti-lipidogenic therapy may be relevant in fibrotic disorders and advanced cancer.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Thüm
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:6599
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