The potential role of macrophage migration inhibitory factor on the migration of vascular smooth muscle cells

The potential role of macrophage migration inhibitory factor on the migration of vascular smooth muscle cells
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DOI:
10.5551/jat.e495
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发表时间:
2008-02-01
影响因子:
4.4
通讯作者:
Koike, Takao
Koike, Takao
中科院分区:
医学2区
文献类型:
--
作者:
Okamoto, Toshiya;Atsumi, Toshiya;Koike, Takao

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目的:巨噬细胞迁移抑制因子(MIF)被称为促炎细胞因子,可调节广泛的炎症反应。 MIF 在血管平滑肌细胞 (VSMC) 中表达,在 MIF 缺陷的动脉粥样硬化小鼠中观察到动脉粥样硬化进展受到抑制。然而,MIF 在 VSMC 中的功能作用尚未阐明。本研究旨在探讨MIF对VSMC迁移的作用。方法:用oxLDL刺激培养的大鼠胚胎主动脉平滑肌细胞A10细胞,分析MIF敲低对oxLDL介导的A10细胞迁移的影响。结果:oxLDL处理的A10细胞上清液中MIF浓度显着增加,细胞内MIF含量显着增加。重组MIF的刺激以剂量依赖性方式显着加速A10细胞的迁移。值得注意的是,通过 siRNA 敲低细胞内 MIF 消除了 oxLDL 诱导的 A10 细胞迁移。结论:这些发现表明,MIF 以自分泌和旁分泌方式作用于 VSMC 的迁移。 MIF 似乎是预防心血管事件的新靶标。
Aim: Macrophage migration inhibitory factor (MIF) is known as a pro-inflammatory cytokine that regulates a broad spectrum of inflammatory reactions. MIF is expressed in vascular smooth muscle cells (VSMCs), and inhibition of the progression of atherosclerosis was observed in MIF-deficient atherosclerotic mice. However, the functional role of MIF in VSMCs has not been elucidated. The aim of this study was to investigate the role of MIF on the migration of VSMCs.Methods: Cultured rat A10 cells, derived from rat embryonic aortic smooth muscle cells, were stimulated with oxLDL, and the effect of MIF knockdown on oxLDL-mediated migration of A10 cells was analyzed.Results: Intracellular MIF content was significantly increased and a marked increase of MIF concentration was observed in the supernatant of A10 cells treated with oxLDL. The migration of A10 cells was significantly accelerated by the stimulation of recombinant MIF in a dose-dependent manner. Notably, knockdown of intracellular MIF by siRNA abolished oxLDL-induced migration of A10 cells.Conclusion: These findings suggest that MIF acts on the migration of VSMCs in an autocrine and paracrine fashion. MIF appears to be a novel target for the prevention of cardiovascular events.