Fornaro, Mara, Hinken, Aaron C., Needle, Saul, Hu, Erding, Trendelenburg, Anne-Ulrike, Meyer, Angelika, Rosenstiel, Antonia, Chang, Calvin, Meier, Viktor, Billin, Andrew N., Becherer, J. David, Evans, William J., Glass, David and Russell, Alan J. (2013) Mechano Growth Factor peptide (MGF), the COOH terminus of unprocessed Insulin-like growth factor 1 (IGF-1), has no apparent effect on muscle myoblasts or primary muscle stem cells. American Journal of Physiology.

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 which 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 pERK, but not pAkt in cardiac myocytes. While 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.

Item Type:	Article
Keywords:	IGF-1, mechano-growth factor, myoblasts, satellite cells
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/10260