Wang Dong, Liu Zhimin, Li Quanyi, Karpurapu Manjula, Kundumani-Sridharan Venkatesh, Cao Huiqing, Dronadula Nagadhara, Rizvi Farhan, Bajpai Arun K, Zhang Chunxiang, Müller-Newen Gerhard, Harris Kevin W, Rao Gadiparthi N
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Circ Res. 2007 Mar 30;100(6):807-16. doi: 10.1161/01.RES.0000261350.61711.9e. Epub 2007 Feb 22.
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.
白细胞介素（IL）-6以剂量依赖的方式诱导血管平滑肌细胞（VSMC）运动。此外，IL-6刺激gp130的酪氨酸磷酸化，导致STAT-3的募集和激活。发现IL-6诱导的VSMC运动依赖于gp130/STAT-3信号的激活。IL-6还以时间和gp130/STAT-3依赖的方式在VSMC中诱导细胞周期蛋白D1表达。通过使用其小干扰RNA分子抑制细胞周期蛋白D1水平可抑制IL-6诱导的VSMC运动。此外，球囊损伤在大鼠颈动脉中诱导IL-6在mRNA和蛋白质水平的表达。球囊损伤还导致STAT-3磷酸化增加和细胞周期蛋白D1表达增加，导致平滑肌细胞从血管中层迁移到内膜区域。通过腺病毒介导的dngp130或dnSTAT-3表达阻断gp130/STAT-3信号，可减弱球囊损伤诱导的STAT-3磷酸化和细胞周期蛋白D1诱导，从而减少平滑肌细胞从血管中层到内膜的迁移并减少新生内膜形成。总之，这些观察结果首次表明IL-6/gp130/STAT-3信号在血管壁重塑中起重要作用，特别是在血管成形术后的情况下，从而在新生内膜形成中起重要作用。
