An essential role for gp130 in neointima formation following arterial injury.
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.
Wang
Dong
D
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Liu
Zhimin
Z
Li
Quanyi
Q
Karpurapu
Manjula
M
Kundumani-Sridharan
Venkatesh
V
Cao
Huiqing
H
Dronadula
Nagadhara
N
Rizvi
Farhan
F
Bajpai
Arun K
AK
Zhang
Chunxiang
C
Müller-Newen
Gerhard
G
Harris
Kevin W
KW
Rao
Gadiparthi N
GN
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*
D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D050822:Cytokine Receptor gp130; D019938:Cyclin D1