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How do your contacts (or their absence) shape your fate?
Emmanuel Charbonney1, Pam Speight1, András Kapus1
1Keenan Research Centre; Li Ka Shing Knowledge Institute; St. Michael's Hospital and Department of Surgery; University of Toronto; Toronto, ON Canada.
Tissue Barriers
|March 26, 2014
Summary
Injury and transforming growth factor-β1 (TGFβ) trigger myofibroblast generation via epithelial-myofibroblast transition (EMyT). A circuit involving β-catenin, Smad3, and MRTF controls α-smooth muscle actin (SMA) expression, influencing healing or fibrosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Pathology
Background:
- Fibrotic diseases are characterized by myofibroblast accumulation.
- Myofibroblast differentiation involves α-smooth muscle actin (SMA) expression.
- Epithelial-myofibroblast transition (EMyT) requires transforming growth factor-β1 (TGFβ) and loss of cell junctions.
Purpose of the Study:
- Investigate the molecular mechanisms of TGFβ synergy with cell contact loss in EMyT.
- Identify key regulators of SMA expression during EMyT.
- Understand the interplay between pretranscriptional and transcriptional control in cellular plasticity.
Main Methods:
- Analysis of transcriptional (co)activators: β-catenin, Smad3, and MRTF.
- Investigation of SMA expression regulation.
- Exploration of pretranscriptional regulatory circuits.
Main Results:
- An interplay between β-catenin, Smad3, and MRTF controls SMA expression magnitude and timing.
- These factors form a pretranscriptional circuit affecting each other's activity and stability.
- Topical susceptibility to TGFβ is mediated by cell contact-modulated control of master regulators.
Conclusions:
- Coordinated action of β-catenin, Smad3, and MRTF dictates SMA expression during EMyT.
- This regulatory network influences the cellular decision between healing and fibrosis.
- Understanding these mechanisms offers insights into fibrotic disease pathogenesis.
Keywords:
Smad3TGFbeta signalngepithelial plasticityepithelial-mesenchymal transitionfibrosismyelofibroblastmyocardin-related transcription facrsmooth muscle actinβ-cateninMore Related Videos
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