Background Recent studies suggest osteopontin (OPN) plays a critical role in the progression of vascular remodelling, and that Urotensin II (UII) is a potent vasoconstrictor and stimulator of cellular migration. The goal of this study was to test the hypothesis that OPN is involved in UII-induced migration of rat aortic adventitial fibroblasts (AFs), and examine the effect and mechanisms of UII on OPN expression.
Design Growth-arrested AFs were incubated in serum-free medium with UII and some inhibitors of signal transduction pathways. Cell migration was determined by a transwell technique. The OPN mRNA expression and protein secretion induced by UII were evaluated by the reverse transcriptase PCR and ELISA method, respectively.
Results OPN antisense oligonucleotides inhibited UII-induced AFs migration significantly compared with UII (10−8 mol/l) group (p<0.05). Moreover, UII promoted the OPN mRNA expression and protein secretion in a dose-dependent and time-dependent manner, with maximal effect at a concentration of 10−8 mol/l at 3 h for mRNA expression, or at 24 h for protein secretion, respectively (p<0.01). The UII receptor antagonist SB710411 (10−6mol/l), Ca2+ channel blocker nicardipine (10−5 mol/l), protein kinase C inhibitor H7 (10−5 mol/l), calcineurin inhibitor cyclosporine A (10−5 mol/l), Rho kinase inhibitor Y-27632 (10−5 mol/l) and mitogen activated protein kinase (MAPK) inhibitor PD98059 (10−5 mol/l) inhibited the UII effects significantly.
Conclusion This study indicated that UII may up-regulate OPN expression in AFs through the UII receptor, protein kinase C, MAPK, calcineurin, Rho kinase and Ca2+ signal transduction pathways, and OPN is involved in UII-induced AFs migration.
- Urotensin II
- adventitial fibroblasts
- vascular remodelling
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