TY - JOUR
T1 - Granulocyte-colony stimulating factor enhances load-induced muscle hypertrophy in mice
AU - Ohashi, Maiko
AU - Okubo, Kazumasa
AU - Mizuno, Sakiko
AU - Yoda, Masaki
AU - Shirasawa, Hideyuki
AU - Chiba, Kazuhiro
AU - Horiuchi, Keisuke
AU - Matsumoto, Morio
AU - Nakamura, Masaya
N1 - Funding Information:
The authors thank Ms. Mika Imamura and Yuri Suzuki for their technical assistance and Dr. Jun Tanihata (The Jikei University School of Medicine, Japan) for his technical advice. This work was partially supported by the General Insurance Association of Japan . The authors declare no competing financial interests.
PY - 2018/12/2
Y1 - 2018/12/2
N2 - Granulocyte-colony stimulating factor (G-CSF) is a cytokine crucially involved in the regulation of granulopoiesis and the mobilization of hematopoietic stem cells from bone marrow. However, emerging data suggest that G-CSF exhibits more diverse functions than initially expected, such as conferring protection against apoptosis to neural cells and stimulating mitogenesis in cardiomyocytes and skeletal muscle stem cells after injury. In the present study, we sought to investigate the potential contribution of G-CSF to the regulation of muscle volume. We found that the administration of G-CSF significantly enhances muscle hypertrophy in two different muscle overload models. Interestingly, there was a significant increase in the transcripts of both G-CSF and G-CSF receptors in the muscles that were under overload stress. Using mutant mice lacking the G-CSF receptor, we confirmed that the anabolic effect is dependent on the G-CSF receptor signaling. Furthermore, we found that G-CSF increases the diameter of myotubes in vitro and induces the phosphorylation of AKT, mTOR, and ERK1/2 in the myoblast-like cell line C2C12 after differentiation induction. These findings indicate that G-CSF is involved in load-induced muscle hypertrophy and suggest that G-CSF is a potential agent for treating patients with muscle loss and sarcopenia.
AB - Granulocyte-colony stimulating factor (G-CSF) is a cytokine crucially involved in the regulation of granulopoiesis and the mobilization of hematopoietic stem cells from bone marrow. However, emerging data suggest that G-CSF exhibits more diverse functions than initially expected, such as conferring protection against apoptosis to neural cells and stimulating mitogenesis in cardiomyocytes and skeletal muscle stem cells after injury. In the present study, we sought to investigate the potential contribution of G-CSF to the regulation of muscle volume. We found that the administration of G-CSF significantly enhances muscle hypertrophy in two different muscle overload models. Interestingly, there was a significant increase in the transcripts of both G-CSF and G-CSF receptors in the muscles that were under overload stress. Using mutant mice lacking the G-CSF receptor, we confirmed that the anabolic effect is dependent on the G-CSF receptor signaling. Furthermore, we found that G-CSF increases the diameter of myotubes in vitro and induces the phosphorylation of AKT, mTOR, and ERK1/2 in the myoblast-like cell line C2C12 after differentiation induction. These findings indicate that G-CSF is involved in load-induced muscle hypertrophy and suggest that G-CSF is a potential agent for treating patients with muscle loss and sarcopenia.
KW - G-CSF
KW - G-CSF receptor
KW - Muscle hypertrophy
KW - Skeletal muscle
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U2 - 10.1016/j.bbrc.2018.10.196
DO - 10.1016/j.bbrc.2018.10.196
M3 - Article
C2 - 30401566
AN - SCOPUS:85055904566
VL - 506
SP - 944
EP - 949
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -