Mighty is a novel promyogenic factor in skeletal myogenesis
Mighty is a novel promyogenic factor in skeletal myogenesis
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DOI：
10.1016/j.yexcr.2008.01.004
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发表时间：
2008-03-10
影响因子：
3.7
通讯作者：
Sharma, Mridula
中科院分区：
文献类型：
--
作者：
Marshall, Amy;Salerno, Monica Senna;Sharma, Mridula
遗传分析揭示了肌生长抑制素（TGF-β超家族成员）在肌发生中的重要功能。然而，响应肌生长抑制素信号传导以调节肌生成的基因级联并不很清楚。因此，抑制性消减杂交，以确定这样的基因进行，在这里，我们报告的一个新的基因，强大的克隆和表征。Mighty在多种不同的组织中表达，但似乎在骨骼肌中受到Myostatin的特异性调节。Mighty在C2 C12细胞中的过表达导致成肌细胞从细胞周期中提前退出，增强和加速肌管的分化和肥大。最重要的是，Mighty过表达导致MyoD的表达增加和更早，以及另一种已知的分化诱导因子IGF-II的分泌增加。此外，Mighty在mdx小鼠中的病毒表达导致较大健康肌肉纤维数量的增加。鉴于其在肌生成中的作用，我们认为Mighty是一种关键的促肌生成因子，在肌生成抑制素下游的信号通路中起关键作用。(C)2008年爱思唯尔公司All rights reserved.
Genetic analysis has revealed an important function in myogenesis for Myostatin, a member of the TGF-beta superfamily. However, the cascade of genes that responds to Myostatin signalling to regulate myogenesis is not well understood. Thus, a suppressive subtraction hybridization to identify such genes was undertaken and here we report the cloning and characterization of a novel gene, Mighty. Mighty is expressed in a variety of different tissues but appears to be specifically regulated by Myostatin in skeletal muscle. Overexpression of Mighty in C2C12 cells results in early withdrawal of myoblasts from the cell cycle, enhanced and accelerated differentiation and hypertrophy of myotubes. Most importantly, Mighty overexpression leads to increased and earlier expression of MyoD and increased secretion of another known differentiation inducing factor, IGF-II. Furthermore, viral expression of Mighty in mdx mice resulted in an increase in the number of larger healthy muscle fibers. Given its role in myogenesis, we propose that Mighty is a critical promyogenic factor which plays a key role in the signalling pathway downstream of Myostatin. (C) 2008 Elsevier Inc. All rights reserved.