c-MET regulates myoblast motility and myocyte fusion during adult skeletal muscle regeneration.

c-MET regulates myoblast motility and myocyte fusion during adult skeletal muscle regeneration.
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DOI:
10.1371/journal.pone.0081757
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Fan CM
Fan CM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Webster MT;Fan CM

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成体肌肉干细胞,即卫星细胞,赋予骨骼肌巨大的再生能力。在损伤后,干细胞作为成肌细胞激活、增殖和迁移到损伤部位,在那里它们成为肌细胞,融合形成新的肌肉。然而,移民是如何受到监管的,在很大程度上仍然不得而知。此外,迁移和融合都需要细胞骨架的动态重排,它们之间可能存在怎样的联系,目前还不清楚。C-Met是一种受体酪氨酸激酶,在胚胎发育过程中,成肌前体细胞迁移到肢体进行肌肉发育是必需的。使用遗传系统消除成年小鼠干细胞中的c-met功能,我们发现c-met是肌肉再生所必需的,以应对急性肌肉损伤。与对照成肌细胞相比,c-met突变的成肌细胞在片状脂体形成方面存在缺陷,迁移范围较短,迁移较慢。令人惊讶的是,c-Met也是有效的肌细胞融合所必需的,这意味着c-Met具有调节成肌细胞迁移和肌细胞融合的双重功能。
Adult muscle stem cells, satellite cells (SCs), endow skeletal muscle with tremendous regenerative capacity. Upon injury, SCs activate, proliferate, and migrate as myoblasts to the injury site where they become myocytes that fuse to form new muscle. How migration is regulated, though, remains largely unknown. Additionally, how migration and fusion, which both require dynamic rearrangement of the cytoskeleton, might be related is not well understood. c-MET, a receptor tyrosine kinase, is required for myogenic precursor cell migration into the limb for muscle development during embryogenesis. Using a genetic system to eliminate c-MET function specifically in adult mouse SCs, we found that c-MET was required for muscle regeneration in response to acute muscle injury. c-MET mutant myoblasts were defective in lamellipodia formation, had shorter ranges of migration, and migrated slower compared to control myoblasts. Surprisingly, c-MET was also required for efficient myocyte fusion, implicating c-MET in dual functions of regulating myoblast migration and myocyte fusion.
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