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首页> 外文期刊>Journal of Cellular Physiology >Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK
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Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK

机译:阿司匹林抑制IL-18-induced心脏成纤维细胞迁移的感应的顾虑

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摘要

The pathogenesis of cardiac fibrosis and adverse remodeling is thought to involve the ROS-dependent induction of inflammatory cytokines and matrix metalloproteinases (MMPs), and the activation and migration of cardiac fibroblasts (CF). Here we investigated the role of RECK (reversion-inducing-cysteine-rich protein with Kazal motifs), a unique membrane-anchored MMP regulator, on IL-18-induced CF migration, and the effect of acetylsalicylic acid (ASA) on this response. In a Matrigel invasion assay, IL-18-induced migration of primary mouse CF was dependent on both IKK/NF-κB- and JNK/AP-1-mediated MMP9 induction and Sp1-mediated RECK suppression, mechanisms that required Nox4-dependent H2O2 generation. Notably, forced expression of RECK attenuated IL-18-induced MMP9 activation and CF migration. Further, therapeutic concentrations of ASA inhibited IL-18-induced H2O2 generation, MMP9 activation, RECK suppression, and CF migration. The salicylic acid moiety of ASA similarly attenuated IL-18-induced CF migration. Thus, ASA may exert potential beneficial effect in cardiac fibrosis through multiple protective mechanisms. J. Cell. Physiol. 229: 845-855, 2014.
机译:心脏纤维化的发病机制和不良重构被认为涉及到ROS-dependent诱导炎性细胞因子和基质金属蛋白酶(MMPs),心脏成纤维细胞的活化和迁移(CF)。(reversion-inducing-cysteine-rich蛋白质与Kazal图案),一个独特的membrane-anchored MMP监管机构,IL-18-induced CF迁移,乙酰水杨酸(ASA)的影响响应。IL-18-induced迁移主要鼠标CF依赖IKK / NF -κB物/ AP-1-mediated MMP9感应和Sp1-mediated介意抑制机制,必需的Nox4-dependent过氧化氢生成。顾虑的表达减弱IL-18-induced MMP9激活和CF迁移。ASA抑制IL-18-induced浓度过氧化氢生成、MMP9激活有关系抑制,CF迁移。一半的ASA同样减毒IL-18-inducedCF迁移。在心脏纤维化有益的影响多重保护机制。229: 845-855, 2014.

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