Transforming Growth Factor-β-Induced Inhibition of Myogenesis Is Mediated Through Smad Pathway and Is Modulated by Microtubule Dynamic Stability

Shoukang Zhu, Pascal J. Goldschmidt-Clermont, Chunming Dong

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The expression of muscle-specific genes associated with myogenesis is controlled by several myogenic transcription factors, including myogenin and MEF2D. Transforming growth factor-β (TGF-β) has been shown to inhibit myogenesis, yet the molecular mechanisms underlying such inhibition are not known. In the present study, TGF-β was shown to inhibit myogenin and MEF2D expression and myotube formation in C2C12 myoblasts cultured in differentiation medium in a cell density-dependent manner. Transfection of C2C12 cells with Smad7, an antagonist for TGF-β/Smad signaling, restored the capacity of these cells to differentiate in the presence of TGF-β or when cultured in growth medium at low confluence, conditions that hinder muscle differentiation. Moreover, nocodazole, a microtubule-destabilizing agent, enhanced the inhibition of myogenesis exerted by TGF-β, an effect that could be restored by tubulin-polymerizing agent taxol, both of which have been shown to affect Smad-microtubule interaction and regulate TGF-β/Smad signaling. Our results indicate that TGF-β inhibits myogenesis, at least in part, via Smad pathway, and provide evidence that low-dose pharmacological agents taxol and nocodazole can be used as a means to modulate myogenesis without affecting cell survival.

Original languageEnglish (US)
Pages (from-to)617-625
Number of pages9
JournalCirculation research
Volume94
Issue number5
DOIs
StatePublished - Mar 19 2004

Keywords

  • Microtubules
  • Myogenesis
  • Signal transduction
  • Smad
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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