Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway.

Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway.
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DOI:
10.1083/jcb.153.2.329
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发表时间:
2001-04-16
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Pavlath GK
Pavlath GK
中科院分区:
其他
文献类型:
--
作者:
Horsley V;Friday BB;Matteson S;Kegley KM;Gephart J;Pavlath GK

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活化T细胞核因子(NFAT)家族转录因子调控多种组织类型的发育和分化。在这里,我们通过分析成年NFATC2 - / -小鼠来研究NFATC2在骨骼肌中的作用。由于肌纤维横截面积的减少,这些小鼠表现出肌肉大小的减少,表明生长变得迟钝。在损伤后再生期间检查肌肉生长,其中nfatc2缺失的肌纤维形成正常,但显示生长受损。生长缺陷是肌肉细胞固有的,因为原代肌肉培养中缺乏NFATC2会导致肌管中细胞大小和肌核数量减少。逆转录病毒介导的NFATC2在突变细胞中的表达挽救了这种细胞表型。在NFATC2−/−小鼠中,我的核数也同样减少。综上所述,这些结果暗示了NFATC2在骨骼肌生长中的新作用。我们证明,在多核肌细胞的生长过程中,成肌细胞最初融合形成具有有限核数的肌管,随后的核添加和肌管大小的增加受到NFATC2调节的分子途径的控制。
The nuclear factor of activated T cells (NFAT) family of transcription factors regulates the development and differentiation of several tissue types. Here, we examine the role of NFATC2 in skeletal muscle by analyzing adult NFATC2−/− mice. These mice exhibit reduced muscle size due to a decrease in myofiber cross-sectional area, suggesting that growth is blunted. Muscle growth was examined during regeneration after injury, wherein NFATC2-null myofibers form normally but display impaired growth. The growth defect is intrinsic to muscle cells, since the lack of NFATC2 in primary muscle cultures results in reduced cell size and myonuclear number in myotubes. Retroviral-mediated expression of NFATC2 in the mutant cells rescues this cellular phenotype. Myonuclear number is similarly decreased in NFATC2−/− mice. Taken together, these results implicate a novel role for NFATC2 in skeletal muscle growth. We demonstrate that during growth of multinucleated muscle cells, myoblasts initially fuse to form myotubes with a limited number of nuclei and that subsequent nuclear addition and increases in myotube size are controlled by a molecular pathway regulated by NFATC2.
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