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Effects of dominant-negative c-Jun on platelet-derived growth factor-induced vascular smooth muscle cell proliferation.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2002 Jan; Vol. 22 (1), pp. 82-8. - Publication Year :
- 2002
-
Abstract
- Although platelet-derived growth factor (PDGF)-BB is thought to participate in vascular disorders, the mechanism of PDGF-induced vascular smooth muscle cell (SMC) proliferation is not fully understood. This study was undertaken to examine the role of c-Jun in PDGF-BB-induced proliferation of rat aortic SMCs. PDGF-BB (10 ng/mL) significantly increased activator protein (AP)-1 DNA binding activity in SMCs, followed by the increase in [(3)H]thymidine incorporation and cell number. SMCs were infected with recombinant adenovirus containing TAM67, a dominant-negative c-Jun lacking the transactivation domain of wild c-Jun (Ad-DN-c-Jun), to inhibit endogenous AP-1. Ad-DN-c-Jun, which specifically blocked AP-1 transcriptional activity, significantly inhibited PDGF-BB-induced increases in [(3)H]thymidine incorporation or cell number. As shown by flow cytometric analysis, Ad-DN-c-Jun inhibited PDGF-BB-induced entrance of SMCs into S phase, leading to a G(1) arrest. Ad-DN-c-Jun attenuated PDGF-BB-induced downregulation of p27(Kip1), as shown by Western blot analysis, and the prevented PDGF-BB-induced decrease in cyclin E/cyclin-dependent kinase 2 complex-associated p27(Kip1), as shown by immunoprecipitation study. Furthermore, protein kinase assay showed that Ad-DN-c-Jun blocked PDGF-BB-induced activation of cyclin-dependent kinase 2. Our results provide the first evidence that dominant-negative c-Jun inhibits PDGF-BB-induced vascular SMC proliferation by preventing the downregulation of p27(Kip1), thereby supporting the important role of c-Jun in vascular SMC proliferation.
- Subjects :
- Animals
Becaplermin
Cell Cycle Proteins metabolism
Cell Division
G1 Phase
Male
Muscle, Smooth, Vascular metabolism
Mutation
Proto-Oncogene Proteins c-jun genetics
Proto-Oncogene Proteins c-sis
Rats
Rats, Sprague-Dawley
Receptors, Platelet-Derived Growth Factor metabolism
Muscle, Smooth, Vascular cytology
Platelet-Derived Growth Factor metabolism
Proto-Oncogene Proteins c-jun physiology
Transcription Factor AP-1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 11788465
- Full Text :
- https://doi.org/10.1161/hq0102.101821