title: Viral expression of insulin-like growth factor I E-peptides increases skeletal muscle mass but at the expense of strength.
abstract: Insulin-like growth factor I (IGF-I) is a protein that regulates and promotes growth in skeletal muscle. The IGF-I precursor polypeptide contains a COOH-terminal extension called the E-peptide. Alternative splicing in the rodent produces two isoforms, IA and IB, where the mature IGF-I in both isoforms is identical yet the E-peptides, EA and EB, share less than 50% homology. Recent in vitro studies show that the E-peptides can enhance IGF-I signaling, leading to increased myoblast cell proliferation and migration. To determine the significance of these actions in vivo and to evaluate if they are physiologically beneficial, EA and EB were expressed in murine skeletal muscle via viral vectors. The viral constructs ensured production of E-peptides without the influence of additional IGF-I through an inactivating mutation in mature IGF-I. E-peptide expression altered ERK1/2 and Akt phosphorylation and increased satellite cell proliferation. EB expression resulted in significant muscle hypertrophy that was IGF-I receptor dependent. However, the increased mass was associated with a loss of muscle strength. EA and EB have similar effects in skeletal muscle signaling and on satellite cells, but EB is more potent at increasing muscle mass. Although sustained EB expression may drive hypertrophy, there are significant physiological consequences for muscle.
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, and Pennsylvania Muscle Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Becky K
authors.initials: BK
authors.lastname: Brisson
authors.forename: Janelle
authors.initials: J
authors.lastname: Spinazzola
authors.forename: SooHyun
authors.initials: S
authors.lastname: Park
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Barton
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000229:Dependovirus; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength / Q000235:genetics*; D018482:Muscle, Skeletal / Q000033:anatomy & histology* / Q000378:metabolism; D009929:Organ Size / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics*
chemical_list: D010446:Peptide Fragments; D007334:Insulin-Like Growth Factor I
keywords: E-peptides; IGF-I; adeno-associated viral vectors; hypertrophy; skeletal muscle