Lysophosphatidic acid and bFGF control different modes in proliferating myoblasts.
Myogenic cells provide excellent in vitro models for studying the cell growth and differentiation. In this study we report that lysophosphatidic acid (LPA), a bioactive phospholipid contained in serum, stimulates the growth and inhibits the differentiation of mouse C2C12 myoblast cells, in a distinct manner from basic fibroblast growth factor (bFGF) whose mitotic and anti-differentiation actions have been well investigated. These actions of LPA were both blocked by pertussis toxin, suggesting the involvement of Gi class of G proteins, whereas bFGF acts through receptor tyrosine kinases. Detailed analysis revealed that LPA and bFGF act differently in regulating the myogenic basic helix-loop-helix (bHLH) proteins, the key players in myogenic differentiation process. LPA stimulates the proliferation of undifferentiated myoblasts allowing the continued expression of MyoD, but in contrast, bFGF does so with the MyoD expression suppressed at the mRNA level. Both compounds maintain the myf-5 expression, and suppress the myogenin expression. In addition, while LPA did not inhibit cell-cell contact-induced differentiation, bFGF strongly inhibited this process. Furthermore, LPA and bFGF act cooperatively in their mitogenic and anti-differentiation abilities. These findings indicate that LPA and bFGF differently stimulate intracellular signaling pathways, resulting in proliferating myoblasts each bearing a distinct expression pattern of myogenic bHLH proteins and distinct differentiation potentials in response to cell-cell contact, and illustrate the biological significance of Gi-mediated and tyrosine kinase-mediated signals.
Yoshida
S
S
Department of Molecular Genetics, National Institute of Neuroscience, Tokyo, Japan.
Fujisawa-Sehara
A
A
Taki
T
T
Arai
K
K
Nabeshima
Y
Y
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D051798:Inhibitor of Differentiation Protein 1; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D024510:Muscle Development; D009132:Muscles / Q000166:cytology / Q000187:drug effects; D017570:MyoD Protein / Q000096:biosynthesis; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D015398:Signal Transduction; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004268:DNA-Binding Proteins; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D008246:Lysophospholipids; D008934:Mitogens; D017570:MyoD Protein; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; D010566:Virulence Factors, Bordetella; D016222:Fibroblast Growth Factor 2; D037342:Pertussis Toxin