Type I insulin-like growth factor receptor signaling in skeletal muscle regeneration and hypertrophy.
Skeletal muscle is able not only to increase its mass as an adaptation to mechanical loading generated by and imposed upon muscle but also to regenerate after damage, via its intrinsic regulation of gene transcription. Both cellular processes, muscle regeneration and hypertrophy, are mediated by the activation, proliferation and differentiation of muscle satellite cells and appear to be modulated by the mitotic and myogenic activity of locally produced insulin-like growth factor 1 (IGF-1), which functions in an autocrine/paracrine mode. Differentiation of satellite cells into myoblasts involves the regulation of skeletal muscle-specific proteins belonging to the family of myogenic regulatory factors (MRFs). The endocrine, autocrine and paracrine functions of IGF-1 are mediated through binding to the type I IGF receptor (IGF-1.R), which is a ligand-activated receptor tyrosine kinase. The binding of IGF-1 to IGF-1.R induces its autophosphorylation, which recruits specific cytoplasmic molecules containing the Insulin Receptor Substrate Proteins (IRS). The recruitment of IRS proteins by IGF-1/IGF-1.R binding is a critical level at which the proliferative and differentiative actions of IGF-1 diverge. Specific signaling pathways downstream of IGF-1, potentially involved in the mitogenic and myogenic responses and mediating skeletal muscle protein synthesis and hypertrophy following exercise-induced muscle overloading and damage, are discussed. A potential alternative activation of different signaling pathway(s) via a different receptor remains to be demonstrated.
Philippou
A
A
Department of Experimental Physiology, Medical School, National and Kapodistrian University of Athens, Goudi-Athens, Greece.
Halapas
A
A
Maridaki
M
M
Koutsilieris
M
M
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1