G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy

Nozomi Hayashiji; Shinsuke Yuasa; Yuko Miyagoe-Suzuki; Mie Hara; Naoki Ito; Hisayuki Hashimoto; Dai Kusumoto; Tomohisa Seki; Shugo Tohyama; Masaki Kodaira; Akira Kunitomi; Shin Kashimura; Makoto Takei; Yuki Saito; Shinichiro Okata; Toru Egashira; Jin Endo; Toshikuni Sasaoka; Shin'ichi Takeda; Keiichi Fukuda

doi:10.1038/ncomms7745

G-CSF supports long-term muscle regeneration in mouse models of muscular dystrophy

Nat Commun. 2015 Apr 13:6:6745. doi: 10.1038/ncomms7745.

Authors

Nozomi Hayashiji¹, Shinsuke Yuasa¹, Yuko Miyagoe-Suzuki², Mie Hara¹, Naoki Ito², Hisayuki Hashimoto¹, Dai Kusumoto¹, Tomohisa Seki¹, Shugo Tohyama¹, Masaki Kodaira¹, Akira Kunitomi¹, Shin Kashimura¹, Makoto Takei¹, Yuki Saito¹, Shinichiro Okata¹, Toru Egashira¹, Jin Endo¹, Toshikuni Sasaoka³, Shin'ichi Takeda², Keiichi Fukuda¹

Affiliations

¹ Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
² Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan.
³ Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.

PMID: 25865621
DOI: 10.1038/ncomms7745

Abstract

Duchenne muscular dystrophy (DMD) is a chronic and life-threatening disease that is initially supported by muscle regeneration but eventually shows satellite cell exhaustion and muscular dysfunction. The life-long maintenance of skeletal muscle homoeostasis requires the satellite stem cell pool to be preserved. Asymmetric cell division plays a pivotal role in the maintenance of the satellite cell pool. Here we show that granulocyte colony-stimulating factor receptor (G-CSFR) is asymmetrically expressed in activated satellite cells. G-CSF positively affects the satellite cell population during multiple stages of differentiation in ex vivo cultured fibres. G-CSF could be important in developing an effective therapy for DMD based on its potential to modulate the supply of multiple stages of regenerated myocytes. This study shows that the G-CSF-G-CSFR axis is fundamentally important for long-term muscle regeneration, functional maintenance and lifespan extension in mouse models of DMD with varying severities.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / drug effects
Cell Division / drug effects
Disease Models, Animal
Gene Expression Regulation
Granulocyte Colony-Stimulating Factor / genetics
Granulocyte Colony-Stimulating Factor / metabolism
Granulocyte Colony-Stimulating Factor / pharmacology*
Longevity / drug effects
Mice
Mice, Inbred mdx
Mice, Knockout
Muscle Cells / drug effects
Muscle Cells / metabolism
Muscle Cells / pathology
Muscle, Skeletal / drug effects*
Muscle, Skeletal / metabolism
Muscle, Skeletal / pathology
Muscular Dystrophy, Duchenne / drug therapy*
Muscular Dystrophy, Duchenne / genetics
Muscular Dystrophy, Duchenne / metabolism
Muscular Dystrophy, Duchenne / pathology
MyoD Protein / genetics
MyoD Protein / metabolism
PAX7 Transcription Factor / genetics
PAX7 Transcription Factor / metabolism
Primary Cell Culture
Receptors, Granulocyte Colony-Stimulating Factor / deficiency
Receptors, Granulocyte Colony-Stimulating Factor / genetics*
Regeneration / drug effects*
Regeneration / genetics
Satellite Cells, Skeletal Muscle / drug effects*
Satellite Cells, Skeletal Muscle / metabolism
Satellite Cells, Skeletal Muscle / pathology
Signal Transduction
Stem Cells / drug effects*
Stem Cells / metabolism
Stem Cells / pathology

Substances

MyoD Protein
MyoD1 myogenic differentiation protein
PAX7 Transcription Factor
Pax7 protein, mouse
Receptors, Granulocyte Colony-Stimulating Factor
Granulocyte Colony-Stimulating Factor