IL-13 mediates the recruitment of reserve cells for fusion during IGF-1-induced hypertrophy of human myotubes.
Insulin-like growth factor-1 (IGF-1) has been shown to induce skeletal muscle hypertrophy, to prevent the loss of muscle mass with ageing and to improve the muscle phenotype of dystrophic mice. We previously developed a model of IGF-1-induced hypertrophy of human myotubes, in which hypertrophy was not only characterized by an increase in myotube size and myosin content but also by an increased recruitment of reserve cells for fusion. Here, we describe a new mechanism of IGF-1-induced hypertrophy by demonstrating that IGF-1 signals exclusively to myotubes but not to reserve cells, leading, under the control of the transcription factor NFATc2, to the secretion of IL-13 that will secondly recruit reserve cells for differentiation and fusion. In addition, we show that IGF-1 also signals to myotubes to stimulate protein metabolism via Akt by (1) activating the mTOR-p70S6K-S6 pathway and inhibiting GSK-3beta, both involved in the control of protein translation, and (2) inhibiting the Foxo1-atrogin-1 protein degradation pathway.
Jacquemin
Virginie
V
UMR S 787, Inserm/UPMC-Paris 6, Institut de Myologie, Paris, France.
Butler-Browne
Gillian Sandra
GS
Furling
Denis
D
Mouly
Vincent
V
D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D018793:Interleukin-13; D011725:Pyridines; D007334:Insulin-Like Growth Factor I; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one