title: Mechano-growth factor peptide, the COOH terminus of unprocessed insulin-like growth factor 1, has no apparent effect on myoblasts or primary muscle stem cells.
abstract: A splice form of IGF-1, IGF-1Eb, is upregulated after exercise or injury. Physiological responses have been ascribed to the 24-amino acid COOH-terminal peptide that is cleaved from the NH3-terminal 70-amino acid mature IGF-1 protein. This COOH-terminal peptide was termed "mechano-growth factor" (MGF). Activities claimed for the MGF peptide included enhancing muscle satellite cell proliferation and delaying myoblast fusion. As such, MGF could represent a promising strategy to improve muscle regeneration. Thus, at our two pharmaceutical companies, we attempted to reproduce the claimed effect of MGF peptides on human and mouse muscle myoblast proliferation and differentiation in vitro. Concentrations of peptide up to 500 ng/ml failed to increase the proliferation of C2C12 cells or primary human skeletal muscle myoblasts. In contrast, all cell types exhibited a proliferative response to mature IGF-1 or full-length IGF-1Eb. MGF also failed to inhibit the differentiation of myoblasts into myotubes. To address whether the response to MGF was lost in these tissue culture lines, we measured proliferation and differentiation of primary mouse skeletal muscle stem cells exposed to MGF. This, too, failed to demonstrate a significant effect. Finally, we tested whether MGF could alter a separate documented in vitro effect of the peptide, activation of p-ERK, but not p-Akt, in cardiac myocytes. Although a robust response to IGF-1 was observed, there were no demonstrated activating responses from the native or a stabilized MGF peptide. These results call in to question whether there is a physiological role for MGF.
authors.affiliation: Novartis Institutes for Biomedical Research, Novartis Pharma, Basel, Switzerland;
authors.forename: Mara
authors.initials: M
authors.lastname: Fornaro
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Hinken
authors.forename: Saul
authors.initials: S
authors.lastname: Needle
authors.forename: Erding
authors.initials: E
authors.lastname: Hu
authors.forename: Anne-Ulrike
authors.initials: AU
authors.lastname: Trendelenburg
authors.forename: Angelika
authors.initials: A
authors.lastname: Mayer
authors.forename: Antonia
authors.initials: A
authors.lastname: Rosenstiel
authors.forename: Calvin
authors.initials: C
authors.lastname: Chang
authors.forename: Viktor
authors.initials: V
authors.lastname: Meier
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Billin
authors.forename: J David
authors.initials: JD
authors.lastname: Becherer
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Brace
authors.forename: William J
authors.initials: WJ
authors.lastname: Evans
authors.forename: David J
authors.initials: DJ
authors.lastname: Glass
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Russell
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D032446:Myoblasts / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: D010446:Peptide Fragments; C523997:mechano-growth factor E, human; D007334:Insulin-Like Growth Factor I
keywords: insulin-like growth factor 1; mechano-growth factor; myoblasts; satellite cells