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miR-155 通过调控 CEH 表达抑制巨噬细胞向泡沫细胞的转化。

MiR-155 inhibits transformation of macrophages into foam cells via regulating CEH expression.

机构信息

Department of Cardiothoracic Surgery, The First Affiliated Hospital of JINZHOU Medical University, Jinzhou, 121001, China.

Department of Cardiothoracic Surgery, The First Affiliated Hospital of JINZHOU Medical University, Jinzhou, 121001, China.

出版信息

Biomed Pharmacother. 2018 Aug;104:645-651. doi: 10.1016/j.biopha.2018.05.068. Epub 2018 May 25.

Abstract

MiR-155 can inhibit the formation of atherosclerosis by interfering with the transformation of macrophages into foam cells that plays a critical role in the pathogenesis of atherosclerosis, but the precise mechanisms of miR-155 are still unknown. Herein, we observed that mRNA and protein expression levels of CEH were significantly upregulated in a dose- and time-dependent manner by transfected with miR-155 mimics in THP-1 macrophages. Further studies showed that overexpression of miR-155 can significantly inhibit foam cells formation, reduce intracellular CE accumulation and enhance the efflux of FC and cholesterol, result in a decrease of intracellular lipid accumulation; while this effect was significantly reversed by siCEH. Meanwhile, we found that Tim-3 is associated with miR-155-mediated CEH expression in THP-1 macrophage-derived foam cells. Overexpression of Tim-3 can attenuate miR-155-mediated CEH induction. Taken together, our findings demonstrated that miR-155 can inhibit the transformation of macrophages into foam cells by enhancing CEH signaling pathway in macrophages, this effect is likely to be achieved by inhibiting the expression of Tim-3.

摘要

miR-155 可以通过干扰巨噬细胞转化为泡沫细胞来抑制动脉粥样硬化的形成,而泡沫细胞在动脉粥样硬化的发病机制中起着关键作用,但 miR-155 的确切机制尚不清楚。在此,我们观察到,用 miR-155 模拟物转染 THP-1 巨噬细胞后,CEH 的 mRNA 和蛋白表达水平呈剂量和时间依赖性显著上调。进一步的研究表明,过表达 miR-155 可以显著抑制泡沫细胞的形成,减少细胞内 CE 的积累,增强 FC 和胆固醇的流出,导致细胞内脂质积累减少;而这一作用被 siCEH 显著逆转。同时,我们发现 Tim-3 与 miR-155 介导的 THP-1 巨噬细胞源性泡沫细胞中 CEH 的表达有关。过表达 Tim-3 可以减弱 miR-155 介导的 CEH 诱导。总之,我们的研究结果表明,miR-155 可以通过增强巨噬细胞中 CEH 信号通路来抑制巨噬细胞向泡沫细胞的转化,这种作用可能是通过抑制 Tim-3 的表达来实现的。

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