Platelet-derived growth factor stimulated vascular smooth muscle cell proliferation and its molecular mechanism.
OBJECTIVE
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.


CONCLUSIONS
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.
Li
J
J
Laboratory of Molecular Pharmacology, Hu-nan Medical University, Changsha 410078, China.
Huang
S L
SL
Guo
Z G
ZG
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001011:Aorta; D000077214:Becaplermin; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D000925:Anticoagulants; D010982:Platelet-Derived Growth Factor; D016271:Proto-Oncogene Proteins c-myc; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000077214:Becaplermin; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1