Roles of ADAM8 in elimination of injured muscle fibers prior to skeletal muscle regeneration

Daigo Nishimura, Hiroshi Sakai, Takahiko Sato, Fuminori Sato, Satoshi Nishimura, Noriko Toyama-Sorimachi, Jörg W. Bartsch, Atsuko Sehara-Fujisawa

研究成果: Article査読

14 被引用数 (Scopus)

抄録

Skeletal muscle regeneration requires processes different from developmental myogenesis. One important difference is a requirement of inflammatory reactions prior to regenerative myogenesis, by which injured muscle fibers must be eliminated to make new myotubes. In this study, we show that efficient elimination of injured muscle fibers during regeneration requires ADAM8, a member of a disintegrin and metalloprotease (ADAM) family. Skeletal muscle of dystrophin-null mice, an animal model for Duchenne Muscular Dystrophy, deteriorates by the lack of ADAM8, which is characterized by increased area of muscle degeneration and increased number of necrotic and calcified muscle fibers. Adam8 is highly expressed in neutrophils. Upon cardiotoxin-induced skeletal muscle injury, neutrophils invade into muscle fibers through the basement membrane and form large clusters in wild type, but not in ADAM8-deficient mice, although neutrophils of the latter infiltrate into interstitial tissues similarly to those of wild type mice. Neutrophils lose their adhesiveness to blood vessels after infiltration, which includes an ectodomain shedding of P-Selectin Glycoprotein Ligand-1 (PSGL-1) on their surface. Expression of PSGL-1 on the surface of neutrophils remains higher in ADAM8-deficient than in wild type mice. These results suggest that ADAM8 mediates an enhanced invasiveness of neutrophils into injured muscle fibers by the removal of their adhesiveness to blood vessels after infiltration into interstitial tissues.

本文言語English
ページ(範囲)58-67
ページ数10
ジャーナルMechanisms of Development
135
DOI
出版ステータスPublished - 01-02-2015
外部発表はい

All Science Journal Classification (ASJC) codes

  • Embryology
  • Developmental Biology

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