title: Mechanical signals and IGF-I gene splicing in vitro in relation to development of skeletal muscle.
abstract: It has been shown that the insulin-like growth factor (IGF-I) gene is spliced in response to mechanical signals producing forms of IGF-I which have different actions. In order to study how mechanical signals influence this gene splicing in developing muscle, C2C12 cells were grown in three-dimensional (3D) culture and subjected to different regimens of mechanical strain. IGF-IEa which initiates the fusion of myoblasts to form myotubes was found to be constitutively expressed in myoblasts and myotubes (held under endogenous tension) and its expression upregulated by a single ramp stretch of 1-h duration but reduced by repeated cyclical stretch. In contrast, mechano growth factor (MGF), which is involved in the proliferation of mononucleated myoblasts that are required for secondary myotube formation and to establish the muscle satellite (stem) cell pool, showed no significant constitutive expression in static cultures, but was upregulated by a single ramp stretch and by cycling loading. The latter types of force simulate those generated in myoblasts by the first contractions of myotubes. These data indicate the importance of seeking to understand the physiological signals that determine the ratios of splice variants of some growth factor/tissue factor genes in the early stages of development of skeletal muscle.
authors.affiliation: Institute of Orthopaedics and Musculo-skeletal Science, University College London, Middlesex, United Kingdom.
authors.forename: Umber
authors.initials: U
authors.lastname: Cheema
authors.forename: Robert
authors.initials: R
authors.lastname: Brown
authors.forename: Vivek
authors.initials: V
authors.lastname: Mudera
authors.forename: Shi Yu
authors.initials: SY
authors.lastname: Yang
authors.forename: Gus
authors.initials: G
authors.lastname: McGrouther
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Goldspink
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D020033:Protein Isoforms; D007334:Insulin-Like Growth Factor I