β2-integrins contribute to skeletal muscle hypertrophy in mice

Joseph S. Marino, Brian J. Tausch, Christopher L. Dearth, Marc V. Manacci, Thomas J. McLoughlin, Samuel J. Rakyta, Matthew P. Linsenmayer, Francis X. Pizza

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)C1026-C1036
JournalAmerican Journal of Physiology - Cell Physiology
Volume295
Issue number4
DOIs
StatePublished - Oct 2008
Externally publishedYes

Keywords

  • Compensatory hypertrophy
  • Macrophages
  • Neutrophils
  • Skeletal muscle growth

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