CD137 signaling induces macrophage M2 polarization in atherosclerosis through STAT6/PPARδ pathway
CD137 signaling induces macrophage M2 polarization in atherosclerosis through STAT6/PPARδ pathway
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CD137信号通路通过STAT6/PPARδ途径诱导动脉粥样硬化中巨噬细胞向M2型极化
DOI：
10.1016/j.cellsig.2020.109628
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发表时间：
2020-08-01
影响因子：
4.8
通讯作者：
Yan, Jin Chuan
中科院分区：
文献类型：
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作者：
Geng, Tianxin;Yan, Yang;Yan, Jin Chuan
CD137信号在动脉粥样硬化斑块的形成和发展中起重要作用。本研究旨在研究CD137信号在动脉粥样硬化中对巨噬细胞极化的影响，并探讨其可能的机制。以载脂蛋白E缺陷小鼠(ApoE-/-)为模型，通过腹腔注射激动剂-CD137重组蛋白，观察CD137信号对动脉粥样硬化斑块巨噬细胞表型的影响。以小鼠腹膜巨噬细胞和RAW 264.7细胞为研究对象，分别用AS1517499和SIPPAR Delta(过氧化物酶体增殖物激活受体Delta)处理，研究信号转导和转录激活因子6(STAT6)/PPAR Delta信号在CD137诱导M2巨噬细胞极化中的作用。体内和体外实验结果表明，CD137信号通路可以在动脉粥样硬化斑块形成过程中将巨噬细胞转化为M2表型，并调节M2巨噬细胞的血管生成特性。此外，CD137信号通路的激活诱导STAT6的磷酸化，并增强PPAR Delta的表达。我们进一步发现，当STAT6/PPAR增量通路被抑制时，巨噬细胞M2极化降低。综上所述，这些数据显示了STAT6/PPAR Delta信号通路在CD137信号诱导的M2巨噬细胞极化通路中的作用。
CD137 signaling plays an important role in the formation and development of atherosclerotic plaques. The purpose of the present study was to investigate the effects of CD137 signaling on macrophage polarization during atherosclerosis and to explore the underlying mechanisms. The effect of CD137 signaling on macrophage phenotype in atherosclerotic plaques was determined by intraperitoneal injection of agonist-CD137 recombinant protein in apolipoprotein E-deficient (ApoE-/-) mice, an established in vivo model of atherosclerosis. Murine peritoneal macrophages and RAW 264.7 cells were treated with AS1517499 and siPPAR delta (peroxisome proliferator-activated receptor delta) to study the role of STAT6 (signal transducers and activators of transcription 6)/PPAR delta signaling in CD137-induced M2 macrophage polarization in vitro. Results from both in vivo and in vitro experiments showed that CD137 signaling can transform macrophages into the M2 phenotype during the process of atherosclerotic plaque formation and regulate the angiogenic features of M2 macrophages. Furthermore, activation of the CD137 signaling pathway induces phosphorylation of STAT6 and enhances the expression of PPAR delta. We further found that macrophage M2 polarization is reduced when the STAT6/PPAR delta pathway is inhibited. Together, these data show a role for the STAT6/PPAR delta signaling pathway in the CD137 signaling-induced M2 macrophage polarization pathway.