Srf-dependent paracrine signals produced by myofibers control satellite cell-mediated skeletal muscle hypertrophy.
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.
Inserm U1016, Institut Cochin, F-75014 Paris, France.
Aline
A
Guerci
Charlotte
C
Lahoute
Sophie
S
Hébrard
Laura
L
Collard
Dany
D
Graindorge
Maryline
M
Favier
Nicolas
N
Cagnard
Sabrina
S
Batonnet-Pichon
Guillaume
G
Précigout
Luis
L
Garcia
David
D
Tuil
Dominique
D
Daegelen
Athanassia
A
Sotiropoulos
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000378:metabolism; D006984:Hypertrophy; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D019899:Paracrine Communication; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000502:physiology; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*
D015850:Interleukin-6; D026362:Serum Response Factor; D015847:Interleukin-4; D051546:Cyclooxygenase 2