title: An essential role for gp130 in neointima formation following arterial injury.
abstract: 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.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Liu
authors.forename: Quanyi
authors.initials: Q
authors.lastname: Li
authors.forename: Manjula
authors.initials: M
authors.lastname: Karpurapu
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Kundumani-Sridharan
authors.forename: Huiqing
authors.initials: H
authors.lastname: Cao
authors.forename: Nagadhara
authors.initials: N
authors.lastname: Dronadula
authors.forename: Farhan
authors.initials: F
authors.lastname: Rizvi
authors.forename: Arun K
authors.initials: AK
authors.lastname: Bajpai
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
authors.forename: Gerhard
authors.initials: G
authors.lastname: Müller-Newen
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Harris
authors.forename: Gadiparthi N
authors.initials: GN
authors.lastname: Rao
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D050822:Cytokine Receptor gp130; D019938:Cyclin D1