title: Beta2-integrins contribute to skeletal muscle hypertrophy in mice.
abstract: We tested the contribution of beta(2)-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 beta-subunit of beta(2)-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 beta(2)-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 beta(2)-integrins contribute to the hypertrophic response to muscle overload by temporally regulating satellite cells/myoblast proliferation and by enhancing muscle differentiation and p70S6k signaling.
authors.affiliation: Department of Kinesiology, The University of Toledo, Toledo, Ohio 43606, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Marino
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Tausch
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Dearth
authors.forename: Marc V
authors.initials: MV
authors.lastname: Manacci
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McLoughlin
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Rakyta
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Linsenmayer
authors.forename: Francis X
authors.initials: FX
authors.lastname: Pizza