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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Transforming growth factor beta1 is up-regulated by activated Raf in skeletal myoblasts but does not contribute to

Xu Wang1, Season R Thomson, Jessica D Starkey

  • 1Department of Poultry Science, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.

The Journal of Biological Chemistry
|November 5, 2003
PubMed

Insights

The Raf/MEK/MAPK pathway impacts skeletal muscle formation. Low Raf activity promotes myogenesis, while high activity and TGF-beta1 inhibit it, revealing complex regulatory roles.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Muscle Development

Background:

  • The Raf/MEK/MAPK pathway negatively impacts skeletal myogenesis, causing loss of muscle gene transcription and differentiation.
  • Raf signaling may also influence myoblast cell cycle exit and cytoprotection.

Purpose of the Study:

  • To investigate the mechanisms of Raf in cellular responses.
  • To define Raf's role in myogenesis and myocyte formation.

Main Methods:

  • Created a stable myoblast cell line (23A2RafER(DD)) expressing an estrogen receptor-Raf chimeric protein.
  • Inducible Raf activity modulation and analysis of downstream signaling (phosphoMAPK).
  • Investigated effects of conditioned medium and TGF-beta1 on myogenesis.

Main Results:

  • Low-level Raf activity enhanced contractile protein expression and myocyte fusion.
  • High-level Raf activity inhibited myocyte formation and muscle reporter gene expression.
  • Conditioned medium from Raf-repressive cells inhibited myogenesis, linked to TGF-beta1 upregulation, but TGF-beta1 inhibition did not restore myogenesis.

Conclusions:

  • Raf signal transmission is involved in both promoting and inhibiting myocyte formation.
  • A TGF-beta1 autocrine loop exists in Raf-repressive myoblasts, but it's not the sole inhibitor of myogenesis.
  • Raf signaling has a complex, dose-dependent role in regulating skeletal myogenesis.

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