Syndecan-1 expression inhibits myoblast differentiation through a basic fibroblast growth factor-dependent mechanism.
Expression of syndecan-1, a cell-surface heparan sulfate proteoglycan, is down-regulated during skeletal muscle differentiation (Larraín, J., Cizmeci-Smith, G., Troncoso, V., Stahl, R. C., Carey, D. J., and Brandan, E. (1997) J. Biol. Chem. 272, 18418-18424). We examined the role of syndecan-1 in basic fibroblast growth factor (bFGF)-dependent inhibition of myogenesis. C2C12 myoblasts were stably transfected with an expression plasmid containing the rat syndecan-1 coding region cDNA. Constitutive syndecan-1 expression resulted in a strongly diminished capacity of the transfected clones to differentiate and to express skeletal muscle-specific markers such as fusion, creatine kinase, and myosin. The expression of myogenin, a master transcription factor for muscle differentiation, was also reduced and delayed. Analysis of the induction of a myogenin promoter-driven reporter revealed that syndecan-1 expression resulted in a 6-7-fold increase in sensitivity to bFGF-dependent inhibition of myogenin expression. Transfecting the cells with a plasmid containing myogenin cDNA reversed the inhibition of myogenin transcriptional activation and myosin expression in syndecan-1-transfected cells; however, cell fusion was not observed. These results demonstrate that syndecan-1 expression enhances cell responsiveness to bFGF and inhibits myoblast fusion and suggest that muscle terminal differentiation is regulated by syndecan-1 expression.
Larraín
J
J
Department of Cell and Molecular Biology, Faculty of Biological Sciences, Catholic University of Chile, Santiago, Chile.
Carey
D J
DJ
Brandan
E
E
D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002459:Cell Fusion; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D003402:Creatine Kinase / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D017930:Genes, Reporter; D015698:Genomic Library; D006493:Heparin / Q000494:pharmacology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D018008:Myogenin / Q000096:biosynthesis / Q000235:genetics; D018995:Myosin Heavy Chains / Q000032:analysis / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D053668:Syndecan-1; D053667:Syndecans; D013997:Time Factors; D014162:Transfection
D015415:Biomarkers; D008562:Membrane Glycoproteins; C503801:Myog protein, mouse; C503803:Myog protein, rat; D018008:Myogenin; D011509:Proteoglycans; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; C508242:Sdc1 protein, mouse; C508243:Sdc1 protein, rat; D053668:Syndecan-1; D053667:Syndecans; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D015500:Chloramphenicol O-Acetyltransferase; C496349:Fgfr1 protein, mouse; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D003402:Creatine Kinase; D018995:Myosin Heavy Chains