Published online before print February 22, 2007, doi: 10.1161/01.RES.0000261350.61711.9e
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Submitted on August 25, 2006
Revised on January 10, 2007
Accepted on January 12, 2007
An Essential Role for gp130 in Neointima Formation Following Arterial Injury
Dong Wang ;
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.
* To whom correspondence should be addressed. 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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