[Role of Rac1 activation in platelet derived growth factor-BB induced proliferation and migration in rat aortic smooth muscle cells].
OBJECTIVE
To explore the impact of Rac1 activation on the proliferation and migration under the stimulation of PDGF-BB (platelet derived growth factor-BB).


METHODS
The inhibitory effects of Rac1 inhibitor (NSC23766) and Rac1siRNA on the proliferation and migration of vascular smooth muscle cell under the stimulation of PDGF-BB were measured by CCK8 assay and Transwell chamber. The time characteristics of Rac1 activity and pi-JNK expression under the stimulation of PDGF-BB was detected by GST pulldown assay and Western blot. And the inhibitory effects of NSC23766 and Rac1siRNA on the Rac1 activation and pi-JNK expression were also measured.


RESULTS
Migration and proliferation of vascular smooth muscle cell increased significantly after the stimulation of PDGF-BB (50 µg/L). Migration and proliferation was inhibited significantly after a pretreatment of Rac1siRNA and various concentrations of NSC23766 (25, 50, 100 µg/L). After the stimulation of PDGF-BB, the expression of pi-JNK and Rac1 activity increased over time. Rac1-GTP peaked at 5 minutes and pi-JNK at 15 minute. The expressions of pi-JNK at 15 minutes and Rac1-GTP at 5 minutes were inhibited significantly by Rac1siRNA and NSC23766 in a concentration-dependent manner.


CONCLUSIONS
JNK phosphorylation is controlled by Rac1 activation. And Rac1 activation play a pivotal role in the migration and proliferation of aortic smooth muscle cell under the stimulation of PDGF-BB.
Sun Yet-Sen University, Guangzhou, China.
Yong
Y
Liu
Yan-zheng
YZ
He
Wen
W
Li
Sen
S
Shi
Zi-lun
ZL
Li
De-yuan
DY
Zhang
Shen-ming
SM
Wang
D000818:Animals; D001011:Aorta / Q000166:cytology; D000077214:Becaplermin; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D000077214:Becaplermin; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein