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Urotensin II induces phenotypic differentiation, migration, and collagen synthesis of adventitial fibroblasts from rat aorta.

Authors: Zhang, YG  Li, J  Li, YG  Wei, RH 
Citation: Zhang YG, etal., J Hypertens. 2008 Jun;26(6):1119-26.
Pubmed: (View Article at PubMed) PMID:18475149
DOI: Full-text: DOI:10.1097/HJH.0b013e3282fa1412

BACKGROUND: Urotensin II is a new potent vasoconstrictor. Nevertheless, little is known about its effects on the activation of adventitial fibroblasts. OBJECTIVE: To explore the effects of urotensin II on phenotypic differentiation, migration, and collagen I synthesis of rat aortic adventitial fibroblasts. METHODS: Growth-arrested adventitial fibroblasts were incubated in serum-free medium with urotensin II and some inhibitors of signal transduction pathways. The alpha-smooth muscle-actin expression, collagen I synthesis and migration of adventitial fibroblasts induced by urotensin II were evaluated by western blot, enzyme-linked immunosorbant assay, and the transwell technique, respectively. RESULTS: Urotensin II induced the [alpha]-smooth muscle-actin expression in a dose-dependent and time-dependent manner, with maximal effect at a concentration of 10(-8) mol/l at 24 h (79.9%); it also caused a dose-dependent increase in collagen I synthesis, with maximal effect at a concentration of 10(-7) mol/l (42.6%). The Ca2+ channel blocker nicardipine (10(-5) mol/l), protein kinase C inhibitor H7 (10(-5) mol/l), Rho protein kinase inhibitor Y-27632 (10(-5) mol/l), calcineurin inhibitor cyclosporine A (10(-5) mol/l), and mitogen-activated protein kinase inhibitor PD98059 (10(-5) mol/l) inhibited urotensin II-induced increases in [alpha]-smooth muscle-actin expression and collagen synthesis. Meanwhile, urotensin II stimulated the migration of adventitial fibroblasts dose dependently, with maximal effect at a concentration of 10(-8) mol/l, which was 5.7-fold greater than that of the control. This effect could also be inhibited by PD98059, H7, cyclosporine A, and Y-27632 but not nicardipine. CONCLUSION: Urotensin II may stimulate adventitial fibroblasts phenotypic conversion, migration, and collagen I synthesis through the protein kinase C, mitogen-activated protein kinase, calcineurin, Rho kinase, and/or Ca2+ signal transduction pathways, contributing to the development of vascular remodeling through adventitial fibroblasts activation.

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RGD Object Information
RGD ID: 2306811
Created: 2009-05-06
Species: All species
Last Modified: 2009-05-06
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.