Myostatin down-regulates the IGF-2 expression via ALK-Smad signaling during myogenesis in cattle

Masato Miyake, Shinichiro Hayashi, Yoshikazu Taketa, Shunsuke Iwasaki, Kouichi Watanabe, Shyuich Ohwada, Hisashi Aso, Takahiro Yamaguchi

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Myostatin (MSTN) is a negative regulator during muscle differentiation, whereas insulin-like growth factors (IGFs) are essential for muscle development. MSTN and IGFs act oppositely during myogenesis, but there is little information on the mutual relationship of MSTN and IGFs. The present study was conducted to examine whether MSTN affects IGF expression during early myogenesis in cattle. IGF-1 mRNA was similarly expressed in M. longissimus thoracis of double-muscled (DM) and normal (NM) Japanese shorthorn cattle. IGF-2 mRNA expression was consistently higher in the normal and regenerating muscle of DM cattle than those of NM cattle. When myoblasts were isolated from regenerating M. longissimus thoracis, IGF-2 mRNA expression showed a significant increase in differentiating DM derived myoblasts (DM-myoblasts) as compared with differentiating NM derived myoblasts (NM-myoblasts). An addition of recombinant mouse myostatin (rMSTN) to myoblast cultures attenuated IGF-2 mRNA expression and decreased myotube formation, but did not effect IGF-1 mRNA expression. An activin-like kinase (ALK) inhibitor, SB431542, mediates MSTN action, suppressed the translocation of Smad2/3 into the nucleus in DM-myoblasts, and restored the attenuated IGF-2 mRNA expression and the decreased myotube formation induced by rMSTN in myoblast cultures. The findings indicate that MSTN may negatively regulate myoblast differentiation by suppressing IGF-2 expression via ALK-Smad signaling.

Original languageEnglish
Pages (from-to)223-229
Number of pages7
JournalAnimal Science Journal
Issue number2
Publication statusPublished - 2010 Apr 1


  • Double-muscled cattle
  • Insulin-like growth factor
  • Myogenesis
  • Myostatin
  • Smad signaling

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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