title: Urotensin II induces phenotypic differentiation, migration, and collagen synthesis of adventitial fibroblasts from rat aorta.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou, China. zhangyg8686@hotmail.com
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Li
authors.forename: Rui-Hong
authors.initials: RH
authors.lastname: Wei
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D019703:Calcineurin / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014579:Urotensins / Q000502:physiology*; D014652:Vascular Diseases / Q000503:physiopathology; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D014579:Urotensins; C029677:urotensin II; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin