IL-17 Stimulates Migration of Carotid Artery Vascular Smooth Muscle Cells in an MMP-9 Dependent Manner via p38 MAPK and ERK1/2-Dependent NF-κB and AP-1 Activation

IL-17 Stimulates Migration of Carotid Artery Vascular Smooth Muscle Cells in an MMP-9 Dependent Manner via p38 MAPK and ERK1/2-Dependent NF-κB and AP-1 Activation
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DOI:
10.1007/s10571-009-9409-z
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发表时间:
2009-12-01
影响因子:
4
通讯作者:
Fu Songbin
Fu Songbin
中科院分区:
医学3区
文献类型:
--
作者:
Gao Cheng;Liu Wei;Fu Songbin

文献摘要

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不适当的血管重塑被认为是血管成形术后再狭窄的主要原因。基质金属蛋白酶(matrix metalloproteinases,MMPs)降解细胞外基质,促进血管平滑肌细胞(vascular smooth muscle cells,VSMC)向管腔内迁移,在病理性血管重塑中发挥重要作用。本研究旨在探讨一种新的细胞因子IL-17对VSMC迁移和MMP-9分泌的影响。从Sprague-Dawley大鼠分离颈动脉VSMC。检测MMP-9的表达、IL-17诱导的细胞迁移及其相关信号通路。结果表明,IL-17以MMP-9依赖的方式诱导VSMC迁移。IL-17通过p38 MAPK和ERK 1/2激活NF-κ B和AP-1诱导MMP-9表达。目前的研究结果表明,IL-17可能在血管重塑中发挥作用,靶向IL-17或其特异性下游介质是减轻血管成形术后再狭窄的潜在新治疗途径。
Inappropriate vascular remodeling is thought to be the main cause of restenosis following angioplasty. Migration of vascular smooth muscle cells (VSMC) into lumina, which is promoted by degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays a causal role in pathological vascular remodeling. The aim of the present research is to explore the effects of a novel cytokine, IL-17, on migration of VSMC and MMP-9 secretion. Carotid artery VSMC was isolated from Sprague-Dawley rats. Expression of MMP-9 and cell migration induced by IL-17 and its related signal pathway were detected. The results showed that IL-17-induced migration of VSMC in an MMP-9-dependent manner. IL-17-induced MMP-9 expression was via p38 MAPK and ERK1/2 dependent NF-kappa B and AP-1 activation. The present results demonstrated that IL-17 may play a role in vascular remodeling and targeting IL-17 or its specific downstream mediators is a potentially novel therapeutic pathway for attenuating the post-angioplastic restenosis.