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Cell Metab. 2012 Jan 4;15(1):25-37. doi: 10.1016/j.cmet.2011.12.001.

Srf-dependent paracrine signals produced by myofibers control satellite cell-mediated skeletal muscle hypertrophy.

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1
Inserm U1016, Institut Cochin, F-75014 Paris, France.

Abstract

Adult skeletal muscles adapt their fiber size to workload. We show that serum response factor (Srf) is required for satellite cell-mediated hypertrophic muscle growth. Deletion of Srf from myofibers and not satellite cells blunts overload-induced hypertrophy, and impairs satellite cell proliferation and recruitment to pre-existing fibers. We reveal a gene network in which Srf within myofibers modulates interleukin-6 and cyclooxygenase-2/interleukin-4 expressions and therefore exerts a paracrine control of satellite cell functions. In Srf-deleted muscles, in vivo overexpression of interleukin-6 is sufficient to restore satellite cell proliferation but not satellite cell fusion and overall growth. In contrast cyclooxygenase-2/interleukin-4 overexpression rescue satellite cell recruitment and muscle growth without affecting satellite cell proliferation, identifying altered fusion as the limiting cellular event. These findings unravel a role for Srf in the translation of mechanical cues applied to myofibers into paracrine signals, which in turn will modulate satellite cell functions and support muscle growth.

PMID:
22225874
DOI:
10.1016/j.cmet.2011.12.001
[Indexed for MEDLINE]
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