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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/C1026    most recent 212.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Marino, J. S. Articles by Pizza, F. X. PubMed PubMed Citation Articles by Marino, J. S. Articles by Pizza, F. X.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

β₂-Integrins contribute to skeletal muscle hypertrophy in mice

Department of Kinesiology, The University of Toledo, Toledo, Ohio

Submitted 17 April 2008 ; accepted in final form 21 August 2008

We tested the contribution of β₂-integrins, which are important for normal function of neutrophils and macrophages, to skeletal muscle hypertrophy after mechanical loading. Using the synergist ablation model of hypertrophy and mice deficient in the common β-subunit of β₂-integrins (CD18^–/–), we found that overloaded muscles of wild-type mice had greater myofiber size, dry muscle mass, and total protein content compared with CD18^–/– mice. The hypertrophy in wild-type mice was preceded by elevations in neutrophils, macrophages, satellite cell/myoblast proliferation (5'-bromo-2'-deoxyuridine- and desmin-positive cells), markers of muscle differentiation (MyoD1 and myogenin gene expression and formation and size of regenerating myofibers), signaling for protein synthesis [phosphorylation of Akt and 70-kDa ribosomal protein S6 kinase (p70S6k)], and reduced signaling for protein degradation (decreased gene expression of muscle atrophy F box/atrogin-1). The deficiency in β₂-integrins, however, altered the accumulation profile of neutrophils and macrophages, disrupted the temporal profile of satellite cell/myoblast proliferation, reduced the markers of muscle differentiation, and impaired the p70S6k signaling, all of which could serve as mechanisms for the impaired hypertrophy in overloaded CD18^–/– mice. In conclusion, our findings indicate that β₂-integrins contribute to the hypertrophic response to muscle overload by temporally regulating satellite cells/myoblast proliferation and by enhancing muscle differentiation and p70S6k signaling.

skeletal muscle growth; neutrophils; macrophages; compensatory hypertrophy