TY - JOUR
T1 - G-CSF influences mouse skeletal muscle development and regeneration by stimulating myoblast proliferation
AU - Hara, Mie
AU - Yuasa, Shinsuke
AU - Shimoji, Kenichiro
AU - Onizuka, Takeshi
AU - Hayashiji, Nozomi
AU - Ohno, Yohei
AU - Arai, Takahide
AU - Hattori, Fumiyuki
AU - Kaneda, Ruri
AU - Kimura, Kensuke
AU - Makino, Shinji
AU - Sano, Motoaki
AU - Fukuda, Keiichi
PY - 2011/4/11
Y1 - 2011/4/11
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20101059
DO - 10.1084/jem.20101059
M3 - Article
C2 - 21422169
AN - SCOPUS:79955706482
SN - 0022-1007
VL - 208
SP - 715
EP - 727
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -