Osteopontin is involved in urotensin II-induced migration of rat aortic adventitial fibroblasts |
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Authors: | Zhang Yong-Gang Kuang Ze-Jian Mao Yan-Yan Wei Rui-Hong Bao Shi-Lin Wu Li-Biao Li Yu-Guang Tang Chao-Shu |
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Institution: | aDepartment of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China;bLaboratory of Molecular Cardiology, First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China;cDepartment of Internal Medicine, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China;dInstitute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China |
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Abstract: | 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 3 h for mRNA expression or at 12 h for protein secretion (both P < 0.01). Furthermore, the UII effects were significantly inhibited by its receptor antagonist SB710411 (10−6 mol/l), and Ca2+ 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 Ca2+ channel, PKC, calcineurin, MAPK and Rho kinase signal transduction pathways. |
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Keywords: | Abbreviations: Ang II angiotensin II CSA cyclosporine A DMEM Dulbecco's modified Eagle's medium ET-1 endothelin-1 MAPK mitogen-activated protein kinase OPN osteopontin PBS phosphate-buffered saline PKC protein kinase C TGF-β1 transforming growth factor-β1 UII urotensin II UT UT receptor (GPR14) VSMCs vascular smooth muscle cells |
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