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Platelet-derived growth factor stimulated vascular smooth muscle cell proliferation and its molecular mechanism
1Laboratory of Molecular Pharmacology, Hu-nan Medical University, Changsha 410078, China.
Aim:
To study the molecular mechanism of platelet-derived growth factor (PDGF)-BB-stimulated vascular smooth muscle cell (VSMC) proliferation.
Methods:
DNA synthesis was measured by [3H]thymidine incorporation. Phosphorylation of the 42- and 44-kDa Ca(2+)-calmodulin dependent protein kinase (CCDPK) was measured by Western blotting method. The expression of c-myc specific mRNA was detected by in situ hybridization.
Results:
PDGF-BB (2 micrograms.L-1) induced DNA synthesis and activated CCDPK in a concentration-dependent manner and a induced a marked c-myc mRNA expression. Egtazic acid (EGTA, 5 mmol.L-1), genistein (400 mumol.L-1) or PD 98059 (50 mumol.L-1) reduced PDGF-BB (2 micrograms.L-1)-induced CCDPK activities and inhibited VSMC [3H]thymidine incorporation (P < 0.05). PD 98059 (50 mumol.L-1) also inhibited PDGF-BB (2 micrograms.L-1)-induced c-myc mRNA expression.
Conclusion:
PDGF stimulated VSMC proliferation by activation of p44/p42 CCDPK, which is mediated by Ca2+ and protein tyrosine kinase (PTK), and up-regulation of c-myc mRNA expression.