Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors.
Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors.
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DOI：
10.1016/j.celrep.2021.109955
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发表时间：
2021-11-02
期刊：
影响因子：
8.8
通讯作者：
Marneros AG
中科院分区：
文献类型：
--
作者：
He L;Jhong JH;Chen Q;Huang KY;Strittmatter K;Kreuzer J;DeRan M;Wu X;Lee TY;Slavov N;Haas W;Marneros AG
M1型和M2型极化的巨噬细胞在细胞代谢和细胞功能上存在显著差异。在这里，全球定量时间进程蛋白质组学和磷蛋白质组学结合转录组学提供了细胞代谢、细胞功能和信号通路在M1型和M2型极化诱导阶段发生的时间变化的全面表征。特别是在代谢途径上观察到显著的差异，包括葡萄糖代谢、糖胺多糖代谢和维甲酸信号的变化。激酶富集化分析显示，在M1型极化和M2型极化中，特定的激酶的激活模式是不同的。M2型极化抑制药物筛选识别选择性阻断M2型极化而不是M1型极化的药物，包括丝裂原激活的蛋白激酶(MEK)和组蛋白脱乙酰酶(HDAC)抑制剂。这些数据集为确定对巨噬细胞极化至关重要的特定信号和代谢途径提供了全面的资源。在一种原则证明的方法中，我们使用这些数据集来证明MEK信号是M2类型极化所必需的，它通过促进过氧化体增殖物激活受体-γ(PPARγ)诱导的维甲酸信号。他等人。利用定量时程蛋白质组学和磷酸蛋白质组学，详细描述巨噬细胞极化过程中细胞信号和代谢的动态时间变化，并确定M2型巨噬细胞极化的药物抑制剂。这些数据揭示了MEK/ERK信号在PPARγ/维甲酸诱导的M2型巨噬细胞极化中的关键作用。
Macrophages undergoing M1- versus M2-type polarization differ significantly in their cell metabolism and cellular functions. Here, global quantitative time-course proteomics and phosphoproteomics paired with transcriptomics provide a comprehensive characterization of temporal changes in cell metabolism, cellular functions, and signaling pathways that occur during the induction phase of M1- versus M2-type polarization. Significant differences in, especially, metabolic pathways are observed, including changes in glucose metabolism, glycosaminoglycan metabolism, and retinoic acid signaling. Kinase-enrichment analysis shows activation patterns of specific kinases that are distinct in M1- versus M2-type polarization. M2-type polarization inhibitor drug screens identify drugs that selectively block M2- but not M1-type polarization, including mitogen-activated protein kinase kinase (MEK) and histone deacetylase (HDAC) inhibitors. These datasets provide a comprehensive resource to identify specific signaling and metabolic pathways that are critical for macrophage polarization. In a proof-of-principle approach, we use these datasets to show that MEK signaling is required for M2-type polarization by promoting peroxisome proliferator-activated receptor-γ (PPARγ)-induced retinoic acid signaling. He et al. provide a detailed characterization of dynamic temporal changes in cell signaling and metabolism during macrophage polarization by using quantitative time-course proteomics and phosphoproteomics and identify pharmacologic inhibitors of M2-type macrophage polarization. These data uncover a critical role of MEK/ERK signaling for PPARγ/retinoic acid-induced M2-type macrophage polarization.
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影响因子：
6
作者：
He, Lizhi;Marneros, Alexander G.
通讯作者：
Marneros, Alexander G.
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia
影响因子：
64.5
作者：
Gosselin D;Link VM;Romanoski CE;Fonseca GJ;Eichenfield DZ;Spann NJ;Stender JD;Chun HB;Garner H;Geissmann F;Glass CK
通讯作者：
Glass CK
影响因子：
20.1
作者：
Chawla A
通讯作者：
Chawla A
影响因子：
7
作者：
Court, Magali;Petre, Graciane;Millet, Arnaud
通讯作者：
Millet, Arnaud