title: TGF-β isoforms inhibit IGF-1-induced migration and regulate terminal differentiation in a cell-specific manner.
abstract: Following muscle injury, the damaged tissue and influx of inflammatory cells stimulate the secretion of growth factors and cytokines to initiate repair processes. This release of chemotactic signaling factors activates resident precursor cells and stimulates their mobilization and migration to the site of injury where terminal differentiation can occur. The three transforming growth factor-β (TGF-β) isoforms, and insulin-like growth factor-1 (IGF-1) are among the known regulatory factors released following muscle damage. We investigated the effect of recombinant active TGF-β1, -β2, -β3 and IGF-1 on C2C12 skeletal muscle satellite cell and P19 embryonal carcinoma cell terminal differentiation and migration. C2C12 myoblast fusion as well as P19 embryoid body formation and myogenic differentiation was assessed following 72 h TGF-β treatment (5 ng/ml), whereas the effect of the TGF-β isoforms on migration was determined following 7 h incubation. Our results showed that TGF-β decreases C2C12 myoblast fusion in an isoform-independent manner, whereas in the P19 cell lineage, results demonstrate that TGF-β1 specifically and significantly increased P19 embryoid body formation, but not expression of Connexin-43 or Myosin Heavy Chain. IGF-1 significantly increased migration compared to TGF-β isoforms, which, on their own, had no significant effect on the mobilization of either C2C12 or P19 cells. TGF-β isoforms decreased IGF-1-induced migration of both cell lineages. By distinguishing the factors involved in, and the molecular signals required for, myoblast recruitment during repair processes, strategies can be developed towards improved cell-mediated therapies for muscle injury.
authors.affiliation: Department of Physiological Sciences, University of Stellenbosch, Private Bag X1, Stellenbosch 7602, South Africa.
authors.forename: Elske J
authors.initials: EJ
authors.lastname: Schabort
authors.forename: Mathilde
authors.initials: M
authors.lastname: van der Merwe
authors.forename: Carola U
authors.initials: CU
authors.lastname: Niesler
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002459:Cell Fusion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects; D009928:Organ Specificity; D020033:Protein Isoforms / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I