An essential role for gp130 in neointima formation following arterial injury
| Autor: | Zhimin Liu, Gerhard Müller-Newen, Quanyi Li, Chunxiang Zhang, Manjula Karpurapu, Huiqing Cao, Gadiparthi N. Rao, Kevin W. Harris, Arun K. Bajpai, Venkatesh Kundumani-Sridharan, Farhan Rizvi, Nagadhara Dronadula, Dong Wang |
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| Rok vydání: | 2007 |
| Předmět: |
Neointima
STAT3 Transcription Factor Vascular smooth muscle Smooth muscle cell migration Physiology Motility Biology Muscle Smooth Vascular chemistry.chemical_compound Cyclin D1 Cell Movement Cytokine Receptor gp130 Animals Cells Cultured Cyclin Interleukin-6 Gene Transfer Techniques Tyrosine phosphorylation Anatomy Cell biology Rats Disease Models Animal chemistry cardiovascular system Phosphorylation Cardiology and Cardiovascular Medicine Carotid Artery Injuries Tunica Intima Signal Transduction Transcription Factors |
| Zdroj: | Circulation research. 100(6) |
| ISSN: | 1524-4571 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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