Myostatin down-regulates the IGF-2 expression via ALK-Smad signaling during myogenesis in cattle
Myostatin down-regulates the IGF-2 expression via ALK-Smad signaling during myogenesis in cattle
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DOI：
10.1111/j.1740-0929.2009.00725.x
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发表时间：
2010-01-01
影响因子：
2
通讯作者：
Yamaguchi, Takahiro
中科院分区：
文献类型：
--
作者：
Miyake, Masato;Hayashi, Shinichiro;Yamaguchi, Takahiro
肌肉生长抑制素（Myostatin，MSTs）是肌肉分化过程中的负调节因子，而胰岛素样生长因子（IGFs）是肌肉发育所必需的。在肌细胞发生过程中，胰岛素样生长因子和胰岛素样生长因子的作用是相反的，但是关于胰岛素样生长因子和胰岛素样生长因子相互关系的信息很少。本研究旨在研究MIBI是否影响牛早期肌发生过程中IGF的表达。IGF-1 mRNA在M.双肌（DM）和正常（NM）日本短角牛的胸最长肌。IGF-2 mRNA的表达始终高于正常和再生肌肉的DM牛比NM牛。从再生的M.在胸最长肌中，与分化中的NM-成肌细胞（NM-成肌细胞）相比，分化中的DM-成肌细胞（DM-成肌细胞）中IGF-2 mRNA表达显示显著增加。此外，重组小鼠肌肉生长抑制素（rMSTO）成肌细胞培养减弱IGF-2 mRNA的表达和减少肌管形成，但不影响IGF-1 mRNA的表达。激活素样激酶（ALK）抑制剂SB 431542介导MclO作用，抑制DM成肌细胞中Smad 2/3易位到细胞核中，并恢复成肌细胞培养物中由rMclO诱导的减弱的IGF-2 mRNA表达和减少的肌管形成。研究结果表明，MIFE可能通过ALK-Smad信号转导抑制IGF-2表达来负调节成肌细胞分化。
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.