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Lysophosphatidic acid and bFGF control different modes in proliferating myoblasts
S Yoshida1, A Fujisawa-Sehara, T Taki
1Department of Molecular Genetics, National Institute of Neuroscience, Tokyo, Japan.
The Journal of Cell Biology
|January 1, 1996
Summary
Lysophosphatidic acid (LPA) stimulates mouse myoblast growth and inhibits differentiation via Gi proteins, distinct from bFGF. LPA and bFGF cooperate, impacting myogenic protein expression differently.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Myogenic cells are key in vitro models for studying cell growth and differentiation.
- Basic fibroblast growth factor (bFGF) is known to stimulate proliferation and inhibit differentiation through receptor tyrosine kinases.
- Lysophosphatidic acid (LPA), a serum phospholipid, also influences cell behavior, but its specific mechanisms in myogenesis are less understood.
Purpose of the Study:
- To investigate and compare the effects of LPA and bFGF on mouse C2C12 myoblast proliferation and differentiation.
- To elucidate the distinct intracellular signaling pathways and myogenic regulatory factor (bHLH) expression patterns modulated by LPA and bFGF.
- To explore the cooperative interactions between LPA and bFGF in regulating myogenesis.
Main Methods:
- Utilized mouse C2C12 myoblast cell cultures as an in vitro model.
- Administered LPA and bFGF to cells and assessed proliferation and differentiation markers.
- Investigated signaling pathways using pertussis toxin (for Gi proteins) and analyzed myogenic basic helix-loop-helix (bHLH) protein expression (MyoD, myf-5, myogenin).
Main Results:
- LPA stimulates myoblast growth and inhibits differentiation, acting through Gi proteins, unlike bFGF which uses receptor tyrosine kinases.
- LPA allows continued MyoD expression during proliferation, while bFGF suppresses it at the mRNA level; both maintain myf-5 and suppress myogenin.
- LPA does not inhibit cell-cell contact-induced differentiation, whereas bFGF does; LPA and bFGF show cooperative effects.
Conclusions:
- LPA and bFGF differentially regulate intracellular signaling pathways in myoblasts.
- Distinct expression patterns of myogenic bHLH proteins and varying differentiation potentials result from LPA and bFGF actions.
- The study highlights the biological significance of Gi-mediated (LPA) and tyrosine kinase-mediated (bFGF) signals in myogenesis.