Myostatin regulates cell survival during C2C12 myogenesis.
During the myogenic process in vitro, proliferating myoblasts withdraw irreversible from the cell cycle, acquire an apoptosis-resistant phenotype, and fuse into mature myotubes. The key factor regulating both myocyte cell cycle exit and viability during this transition is the the cyclin-dependent kinase inhibitor p21(cip1). Here we show that the expression of myostatin, a TGF-beta superfamily member known to act as a negative regulator of muscle growth, is upregulated in the course of C2C12 cells myogenesis. We also show that transient transfection of C2C12 myobasts with an expression vector encoding mouse myostatin cDNA efficiently inhibits cell proliferation. Paradoxically, myostatin cDNA overexpression also enhances the survival of differentiating C2C12 myocytes, probably by a mechanism involving, at least in part, upregulation of p21(cip1) mRNA. Our results suggest that myostatin role in myogenesis is more complex than initially suggested and involves another level of regulation apart from inhibition of myoblast proliferation.
Ríos
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Departamento de Fisiología and Facultad de Medicina, Universidad de Santiago de Compostela, San Francisco s/n, Santiago de Compostela, 15705, Spain.
Carneiro
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Arce
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Devesa
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J
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D051379:Mice; D009132:Muscles / Q000166:cytology* / Q000378:metabolism; D055435:Myostatin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C525912:Mstn protein, mouse; D055435:Myostatin; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta