Osteopontin is involved in urotensin II-induced migration of rat aortic adventitial fibroblasts.
Recent studies suggest that both osteopontin and urotensin II (UII) play critical roles in vascular remodeling. We previously showed that UII could stimulate the migration of aortic adventitial fibroblasts. In this study, we examined whether osteopontin is involved in UII-induced migration of rat aortic adventitial fibroblasts and examined the effects and mechanisms of UII on osteopontin expression in adventitial fibroblasts. Migration of adventitial fibroblasts induced by UII could be inhibited significantly by osteopontin antisense oligonucleotide (P<0.01) but not sense or mismatch oligonucleotides (P>0.05). Moreover, UII dose- and time-dependently promoted osteopontin mRNA expression and protein secretion in the cells, with maximal effect at 10(-8)mol/l at 3h for mRNA expression or at 12h for protein secretion (both P<0.01). Furthermore, the UII effects were significantly inhibited by its receptor antagonist SB710411 (10(-6)mol/l), and Ca(2+) channel blocker nicardipine (10(-5)mol/l), protein kinase C (PKC) inhibitor H7 (10(-5)mol/l), calcineurin inhibitor cyclosporine A (10(-5)mol/l), mitogen-activated protein kinase (MAPK) inhibitor PD98059 (10(-5)mol/l) and Rho kinase inhibitor Y-27632 (10(-5)mol/l). Thus, osteopontin is involved in the UII-induced migration of adventitial fibroblasts, and UII could upregulate osteopontin gene expression and protein synthesis in rat aortic adventitial fibroblasts by activating its receptor and the Ca(2+) channel, PKC, calcineurin, MAPK and Rho kinase signal transduction pathways.
Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China. zhangyg8686@hotmail.com
Yong-Gang
YG
Zhang
Ze-Jian
ZJ
Kuang
Yan-Yan
YY
Mao
Rui-Hong
RH
Wei
Shi-Lin
SL
Bao
Li-Biao
LB
Wu
Yu-Guang
YG
Li
Chao-Shu
CS
Tang
D000577:Amides / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002465:Cell Movement; D003470:Culture Media / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009841:Oligonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D053495:Osteopontin / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013997:Time Factors; D014579:Urotensins / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000577:Amides; D015220:Calcium Channels; D003470:Culture Media; D005419:Flavonoids; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011725:Pyridines; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C506897:Spp1 protein, rat; D014579:Urotensins; C473142:Uts2r protein, rat; D053495:Osteopontin; C108830:Y 27632; D016572:Cyclosporine; C029677:urotensin II; D009529:Nicardipine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one