Myostatin down‐regulates the IGF‐2 expression via ALK‐Smad signaling during myogenesis in cattle |
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Authors: | Masato MIYAKE Shinichiro HAYASHI Yoshikazu TAKETA Shunsuke IWASAKI Kouichi WATANABE Shyuich OHWADA Hisashi ASO Takahiro YAMAGUCHI |
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Affiliation: | 1. Department of Animal Biology, Graduate School of Agricultural Science, Tohoku University, Aoba, Sendai, Japan;2. Present address: Mouse Molecular Genetics group, UMR S 787 – Groupe Myologie, INSERM – UPMC‐Paris VI, 75634 – Paris Cedex 13 France. |
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Abstract: | 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. |
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Keywords: | double‐muscled cattle insulin‐like growth factor myogenesis myostatin Smad signaling |
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