Expression profiling of cytokines and related genes in regenerating skeletal muscle after cardiotoxin injection: a role for osteopontin.
To examine the roles of cytokines in muscle regeneration, we injected cardiotoxin into mouse tibialis anterior muscle and examined the expression profiles of cytokines and related genes in the regeneration process. Expression of 40, 64, and 7 genes among 522 genes spotted on a cytokine expression array were increased more than fivefold at 48 hours, 96 hours, and 7 days after toxin injection, respectively, when compared with those of the control muscle. Especially the levels of mRNA for chemokines and chemokine receptors, many of which are potent regulators of macrophages, were highly elevated 48 hours after injury. The expression of osteopontin (OPN), a versatile regulator of inflammation and tissue repair, was up-regulated more than 118-fold in regenerating muscle at 48 hours after injury. Northern blotting confirmed that the expression of OPN was highest at 48 hours after cardiotoxin injection and declined sharply thereafter. Immunohistochemistry showed that OPN was detected both in the cytoplasm of macrophages and in necrotic muscle infiltrated with macrophages. Our studies suggest OPN may serve as an adhesion molecule that promotes macrophage binding to necrotic fibers and may be an important mediator in the early phase of muscle regeneration.
Hirata
Akira
A
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Masuda
Satoru
S
Tamura
Tetsuo
T
Kai
Kazuko
K
Ojima
Koichi
K
Fukase
Akiko
A
Motoyoshi
Kazuo
K
Kamakura
Keiko
K
Miyagoe-Suzuki
Yuko
Y
Takeda
Shin'ichi
S
D000818:Animals; D004179:Cobra Cardiotoxin Proteins / Q000008:administration & dosage / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism
D004179:Cobra Cardiotoxin Proteins; D016207:Cytokines; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin