G-CSF influences mouse skeletal muscle development and regeneration by stimulating myoblast proliferation
G-CSF influences mouse skeletal muscle development and regeneration by stimulating myoblast proliferation
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DOI：
10.1084/jem.20101059
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发表时间：
2011-04-11
影响因子：
15.3
通讯作者：
Fukuda, Keiichi
中科院分区：
文献类型：
--
作者：
Hara, Mie;Yuasa, Shinsuke;Fukuda, Keiichi
骨骼肌损伤后，中性粒细胞、单核细胞和巨噬细胞浸润受损区域;随后是来自肌肉干细胞（也称为卫星细胞）的成肌细胞的快速增殖。虽然炎症触发骨骼肌再生是已知的，但其潜在的分子机制仍不完全清楚。在这项研究中，我们表明，粒细胞集落刺激因子（G-CSF）受体（G-CSFR）在发育体节表达。G-CSFR和G-CSF在妊娠中期的小鼠胚胎成肌细胞中表达，而在成熟的心肌细胞中不表达。此外，G-CSFR特异性但瞬时表达于损伤的成年小鼠骨骼肌中存在的再生肌细胞中。用封闭抗体中和内源性G-CSF损害了再生过程，而外源性G-CSF通过促进再生成肌细胞的增殖来支持肌肉再生。此外，在G-CSFR敲除小鼠中，肌肉再生明显受损。这些发现表明G-CSF对骨骼肌细胞发育和再生至关重要，并证明了炎症介导的肌肉再生诱导的重要性。
After skeletal muscle injury, neutrophils, monocytes, and macrophages infiltrate the damaged area; this is followed by rapid proliferation of myoblasts derived from muscle stem cells (also called satellite cells). Although it is known that inflammation triggers skeletal muscle regeneration, the underlying molecular mechanisms remain incompletely understood. In this study, we show that granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) is expressed in developing somites. G-CSFR and G-CSF were expressed in myoblasts of mouse embryos during the midgestational stage but not in mature myocytes. Furthermore, G-CSFR was specifically but transiently expressed in regenerating myocytes present in injured adult mouse skeletal muscle. Neutralization of endogenous G-CSF with a blocking antibody impaired the regeneration process, whereas exogenous G-CSF supported muscle regeneration by promoting the proliferation of regenerating myoblasts. Furthermore, muscle regeneration was markedly impaired in G-CSFR-knockout mice. These findings indicate that G-CSF is crucial for skeletal myocyte development and regeneration and demonstrate the importance of inflammation-mediated induction of muscle regeneration.