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Title of article :
Indole-3-carbinol blocks platelet-derived growth factor-stimulated vascular smooth muscle cell function and reduces neointima formation in vivo
Author/Authors :
Hongjing Guan، نويسنده , , Changgui Chen، نويسنده , , Lihua Zhu، نويسنده , , Changping Cui، نويسنده , , Yuanyuan Guo، نويسنده , , Mingyue Fu، نويسنده , , Lang Wang، نويسنده , , Qizhu Tang، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2013
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Abstract :
The purpose of this study was to determine the effect and associated cell signaling mechanisms of indole-3-carbinol (I3C) on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of cultured vascular smooth muscle cells (VSMCs) and neointima formation in a carotid injury model. Our data demonstrated that I3C inhibited PDGF-BB-induced proliferation of VSMCs in a dose-dependent manner without causing cell cytotoxicity, as assessed by 5-bromo-2′-deoxyuridine incorporation and WST-1 assays. Further studies revealed that the antiproliferative effect of I3C was caused by the arrest of cells in both the G0/G1 and S phases. Moreover, I3C treatment inhibited migration of VSMCs and partly reversed the expression of smooth-muscle-specific contractile markers. We also demonstrated that I3C-induced growth inhibition was associated with an inhibition of the expression of cyclin D1 and cyclin-dependent kinase 4/6, as well as an increase in p27Kip1 levels in PDGF-stimulated VSMCs. These beneficial effects of I3C on VSMCs appeared to be at least partly mediated by the inhibition of Akt and the subsequent activation of glycogen synthase kinase (GSK) 3β. Furthermore, using a mouse carotid artery injury model, we found that treatment with 150 mg/kg I3C resulted in a significant reduction of the neointima/media ratio and cells positive for proliferating cell nuclear antigen. These results demonstrate that I3C can suppress the proliferation and migration of VSMCs and neointima hyperplasia after vascular injury via inhibition of the Akt/GSK3β pathway and suggest that this might be feasible as part of a therapeutic strategy for vascular proliferative diseases.
Keywords :
Indole-3-carbinol , Neointima , Vascular smooth muscle cell , Platelet-derived growth factor
Journal title :
The Journal of Nutritional Biochemistry
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