Minireview: Mechano-Growth Factor: A Putative Product of IGF-I Gene Expression Involved in Tissue Repair and Regeneration

摘要

The discovery that IGF-I mRNAs encoding isoforms of the pro-IGF-I molecule are differentially regulated in response to mechanical stress in skeletal muscle has been theimpetus for a number of studies designed to demonstrate that alternative splicing of IGF-I pre-mRNA involving exons 4, 5, and 6 gives rise to a unique peptide derivedfrom pro-IGF-I that plays a novel role in myoblast proliferation. Research suggests that after injury to skeletal muscle, the IGF-IEb mRNA splice variant is up-regulatedinitially, followed by up-regulation of the IGF-IEa splice variant at later time points. Up-regulation of IGF-IEb mRNA correlates with markers of satellite cell and myoblastproliferation,whereasup-regulationofIGF-IEamRNAiscorrelatedwithdifferentiationtomaturemyofibers.DuetotheapparentroleofIGF-IEbup-regulationinmuscleremodeling, IGF-IEb mRNA was also named mechano-growth factor (MGF). A synthetically manufactured peptide (also termed MGF) corresponding to the 24 mostC-terminalresiduesofIGF-IEbhasbeenshowntopromotecellularproliferationandsurvival.However,noanalogouspeptideproductoftheIgf1genehasbeenidentifiedin or isolated from cultured cells, their conditioned medium, or in vivo animal tissues or biological fluids. This review will discuss the relationship of the Igf1 gene to MGFand will differentiate actions of synthetic MGF from any known product of Igf1. Additionally, the role of MGF in satellite cell activation, aging, neuroprotection, andsignaling will be discussed. A survey of outstanding questions relating to MGF will also be provided.