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

Shoukang Zhu, Pascal Goldschmidt-Clermont, Chunming Dong

Research output: Contribution to journalArticle

58 Citations (Scopus)

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
Pages (from-to)617-625
Number of pages9
JournalCirculation Research
Volume94
Issue number5
DOIs
StatePublished - Mar 19 2004
Externally publishedYes

Fingerprint

Muscle Development
Transforming Growth Factors
Microtubules
Myogenin
Nocodazole
Paclitaxel
Muscles
Myoblasts
Skeletal Muscle Fibers
Tubulin
Transfection
Cell Survival
Transcription Factors
Cell Count
Pharmacology
Growth
Genes

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Transforming Growth Factor-β-Induced Inhibition of Myogenesis Is Mediated Through Smad Pathway and Is Modulated by Microtubule Dynamic Stability. / Zhu, Shoukang; Goldschmidt-Clermont, Pascal; Dong, Chunming.

In: Circulation Research, Vol. 94, No. 5, 19.03.2004, p. 617-625.

Research output: Contribution to journalArticle

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