RGD Reference Report - Urotensin II induces phenotypic differentiation, migration, and collagen synthesis of adventitial fibroblasts from rat aorta. - Rat Genome Database

RGD Reference Report - Urotensin II induces phenotypic differentiation, migration, and collagen synthesis of adventitial fibroblasts from rat aorta. - Rat Genome Database

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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.
RGD ID:	2306811
Pubmed:	PMID:18475149 (View Abstract at PubMed)
DOI:	DOI:10.1097/HJH.0b013e3282fa1412 (Journal Full-text)
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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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
positive regulation of cell differentiation		IDA		2306811		RGD
positive regulation of collagen biosynthetic process		IDA		2306811		RGD
positive regulation of fibroblast migration		IDA		2306811		RGD

Objects Annotated

Genes (Rattus norvegicus)

Uts2 (urotensin 2)

Objects referenced in this article

Gene	Anxa1	annexin A1	Rattus norvegicus

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