Cited by 229

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Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors.

Allen, David L., Unterman, Terry G.·2007·American Journal of Physiology-Cell Physiology

Abstract

Myostatin, a member of the transforming growth factor (TGF)-β family, plays an important role in regulating skeletal muscle growth and differentiation. Here we examined the role of FoxO1 and SMAD transcription factors in regulating myostatin gene expression and myoblast differentiation in C 2 C 12 myotubes in vitro. Both myostatin and FoxO1 mRNA expression were greater in fast- vs. slow-twitch skeletal muscles in vivo. Moreover, expression of a constitutively active form of FoxO1 increased myostatin mRNA and increased activity of a myostatin promoter reporter construct in differentiated C 2 C 12 myotubes. Mutagenesis of highly conserved FoxO or SMAD binding sites significantly decreased myostatin promoter activity, and binding assays showed that both FoxO1 and SMADs bind to their respective sites in the myostatin promoter. Treatment with TGF-β and/or overexpression of SMAD2, -3, or -4 also resulted in a significant increase in myostatin promoter activity. Treatment with TGF-β along with overexpression of SMAD2 and FoxO1 resulted in the largest increase in myostatin promoter activity. Finally, TGF-β treatment and SMAD2 overexpression greatly potentiated FoxO1-mediated suppression of myoblast differentiation. Together these data demonstrate that FoxO1 and SMAD transcription factors regulate the expression of myostatin and contribute to the control of muscle cell growth and differentiation.

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Crossref · 10.1152/ajpcell.00542.2005

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Research works printed but not linked: 38

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Metadata

Authors
Allen, D. L., & Unterman, T. G.
Venue
American Journal of Physiology-Cell Physiology
Published
2007-01
Volume
292
Issue
1
Pages
C188-C199
ISSN
  • 0363-6143
  • 1522-1563
Cited by
229
References
8
Language
en

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