Published online before print February 22, 2007, doi: 10.1161/01.RES.0000261350.61711.9e
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© 2007 American Heart Association, Inc.
Molecular Medicine |
An Essential Role for gp130 in Neointima Formation Following Arterial Injury
From the Departments of Physiology (D.W., Z.L., Q.L., M.K., V.K.-S., H.C., N.D., F.R., A.K.B., G.N.R.) and Surgery (C.Z.), University of Tennessee Health Science Center, Memphis; Institut fur Biochemie (G.M.-N.), Rheinisch-Westflische Technische Hochschule Aachen, Germany; and Division of Hematology (K.W.H.), Department of Medicine, University of Alabama at Birmingham.
Correspondence to Gadiparthi N. Rao, PhD, Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163. E-mail grao{at}physio1.utmem.edu
Interleukin (IL)-6 induced vascular smooth muscle cell (VSMC) motility in a dose-dependent manner. In addition, IL-6 stimulated tyrosine phosphorylation of gp130, resulting in the recruitment and activation of STAT-3. IL-6–induced VSMC motility was found to be dependent on activation of gp130/STAT-3 signaling. IL-6 also induced cyclin D1 expression in a time- and gp130/STAT-3–dependent manner in VSMCs. Suppression of cyclin D1 levels via the use of its small interfering RNA molecules inhibited IL-6–induced VSMC motility. Furthermore, balloon injury induced IL-6 expression both at mRNA and protein levels in rat carotid artery. Balloon injury also caused increased STAT-3 phosphorylation and cyclin D1 expression, leading to smooth muscle cell migration from the media to the intimal region. Blockade of gp130/STAT-3 signaling via adenovirus-mediated expression of dngp130 or dnSTAT-3 attenuated balloon injury–induced STAT-3 phosphorylation and cyclin D1 induction, resulting in reduced smooth muscle cell migration from media to intima and decreased neointima formation. Together, these observations for the first time suggest that IL-6/gp130/STAT-3 signaling plays an important role in vascular wall remodeling particularly in the settings of postangioplasty and thereby in neointima formation.
Key Words: cyclin D1 • cytokines • migration • smooth muscle cells • transcription factors
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