Serum and fibroblast growth factor inhibit myogenic differentiation through a mechanism dependent on protein synthesis and independent of cell proliferation.
Myogenesis is accompanied by the withdrawal of proliferating myoblasts from the cell cycle, their fusion to form myotubes, and the coordinate expression of a variety of muscle-specific gene products, such as the muscle isoenzyme of creatine kinase (MCK). In the present study we used the nonfusing muscle cell line, BC3H1, to examine the mechanisms involved in regulation of MCK mRNA expression. Proliferating BC3H1 cells, in media with 20% fetal calf serum, had undetectable levels of MCK mRNA. Exposure of undifferentiated cells to media containing 0.5% serum resulted in withdrawal of cells from the cell cycle and in a several hundred-fold increase in the steady state level of MCK mRNA. Induction of this muscle-specific mRNA could be rapidly reversed by exposure of quiescent differentiated cells to media containing either 20% serum or pituitary fibroblast growth factor. The decline in the steady state level of MCK mRNA following mitogenic stimulation was not dependent upon reentry of cells into the cell cycle, but it did require protein synthesis. Together, these data indicate that fibroblast growth factor can specifically inhibit muscle-specific gene expression through a mechanism independent of cell proliferation. The finding that MCK mRNA was down-regulated by a mechanism that required protein synthesis suggests that mitogen-inducible early gene products may be involved in regulation of muscle gene expression.
D000818:Animals; D001769:Blood; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D003402:Creatine Kinase / Q000235:genetics*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007527:Isoenzymes; D007700:Kinetics; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*
D007527:Isoenzymes; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D003402:Creatine Kinase; D009955:Ornithine Decarboxylase