Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle.
Insulin-like growth factor I (IGF-I) is a critical protein for skeletal muscle development and regeneration. Its ability to promote skeletal muscle hypertrophy has been demonstrated by several methods. Alternative splicing of the Igf-1 gene does not affect the mature IGF-I protein but does produce different E peptide extensions, which have been reported to modify the potency of IGF-I. Viral-mediated delivery of murine IGF-IA and IGF-IB into skeletal muscle of 2-wk-old and 6-mo-old mice was utilized to compare the effects of the isoforms on muscle mass. In young mice, tissue content of IGF-I protein was significantly higher in rAAV-treated muscles than control muscles at 1, 2, and 4 mo postinjection. Viral injection of IGF-IB produced two- to sevenfold more IGF-I than rAAVIGF-IA. Hypertrophy was observed 2 and 4 mo postinjection, where both rAAVIGF-IA and rAAVIGF-IB were equally effective in increasing muscle mass. These results suggest that there is a threshold of IGF-I production necessary to promote muscle hypertrophy in young growing animals regardless of isoform. In 6-mo-old animals, only rAAVIGF-IA produced significant increases in muscle size, even though increased IGF-I content was observed after injection of both isoforms. Therefore, the ability for IGF-IB to promote muscle hypertrophy is only effective in growing animals, suggesting that the bioavailability of this isoform or its receptor affinity diminishes with age.
Barton
Elisabeth R
ER
Department of Anatomy and Cell Biology, 441A Levy Bldg., 240 S. 40th St., University of Pennsylvania, Philadelphia, PA 19104, USA. erbarton@biochem.dental.upenn.edu
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D015967:Gene Expression Regulation, Viral; D006984:Hypertrophy / Q000473:pathology / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000502:physiology* / Q000821:virology; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000502:physiology; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D019076:Transgenes / Q000235:genetics / Q000502:physiology
D020033:Protein Isoforms; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1