ADAM12 alleviates the skeletal muscle pathology in mdx dystrophic mice.
Muscular dystrophy is characterized by muscle degeneration and insufficient regeneration and replacement of muscle fibers by connective tissue. New therapeutic strategies directed toward various forms of muscular dystrophy are needed to preserve muscle mass and promote regeneration. In this study we examined the role of the transmembrane ADAM12, a disintegrin and metalloprotease, which is normally associated with development and regeneration of skeletal muscle. We demonstrate that ADAM12 overexpression in the dystrophin-deficient mdx mice alleviated the muscle pathology in these animals, as evidenced by less muscle cell necrosis and inflammation, lower levels of serum creatine kinase, and less uptake of Evans Blue dye into muscle fibers. These studies demonstrate that ADAM12 directly or indirectly contributes to muscle cell regeneration, stability, and survival.
Kronqvist
Pauliina
P
Institute of Molecular Pathology, University of Copenhagen, Denmark.
Kawaguchi
Nobuko
N
Albrechtsen
Reidar
R
Xu
Xiufeng
X
Schrøder
Henrik Daa
HD
Moghadaszadeh
Behzad
B
Nielsen
Finn Cilius
FC
Fröhlich
Camilla
C
Engvall
Eva
E
Wewer
Ulla M
UM
D051722:ADAM Proteins; D000072199:ADAM12 Protein; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000473:pathology*; D009136:Muscular Dystrophies / Q000473:pathology*; D009336:Necrosis
D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D008666:Metalloendopeptidases