Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy.
Skeletal muscles adapt to increasing workload by augmenting their fiber size, through mechanisms that are poorly understood. This study identifies the cytokine interleukin-6 (IL-6) as an essential regulator of satellite cell (muscle stem cell)-mediated hypertrophic muscle growth. IL-6 is locally and transiently produced by growing myofibers and associated satellite cells, and genetic loss of IL-6 blunted muscle hypertrophy in vivo. IL-6 deficiency abrogated satellite cell proliferation and myonuclear accretion in the preexisting myofiber by impairing STAT3 activation and expression of its target gene cyclin D1. The growth defect was indeed muscle cell intrinsic, since IL-6 loss also affected satellite cell behavior in vitro, in a STAT3-dependent manner. Myotube-produced IL-6 further stimulated cell proliferation in a paracrine fashion. These findings unveil a role for IL-6 in hypertrophic muscle growth and provide mechanistic evidence for the contribution of satellite cells to this process.
Serrano
Antonio L
AL
Program on Differentiation and Cancer, Center for Genomic Regulation (CRG) and Center for Neurodegenerative Diseases (CIBERNED), Pompeu Fabra University, Barcelona, Spain.
Baeza-Raja
Bernat
B
Perdiguero
Eusebio
E
Jardí
Mercè
M
Muñoz-Cánoves
Pura
P
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006984:Hypertrophy; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000473:pathology
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D019938:Cyclin D1