Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors
| Autor: | Qi Chen, Michael DeRan, Kai-Yao Huang, Johannes Kreuzer, Xu Wu, Jhih-Hua Jhong, Karin Strittmatter, Lizhi He, Tzong-Yi Lee, Alexander G. Marneros, Wilhelm Haas, Nikolai Slavov |
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| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Time Factors Proteome THP-1 Cells QH301-705.5 macrophage polarization Macrophage polarization Retinoic acid Tretinoin Proof of Concept Study Article General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound MEK signaling Animals Humans Phosphorylation Biology (General) retinoic acid signaling Protein kinase A Protein Kinase Inhibitors M1-type polarization Mitogen-Activated Protein Kinase Kinases Kinase Chemistry Macrophages Phosphoproteomics phosphoproteomics Macrophage Activation Cell biology Histone Deacetylase Inhibitors Mice Inbred C57BL PPAR gamma M2-type polarization Phenotype Interleukin-4 Histone deacetylase Signal transduction Energy Metabolism Signal Transduction |
| Zdroj: | Cell Reports, Vol 37, Iss 5, Pp 109955-(2021) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. In brief 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. Graphical Abstract |
| Databáze: | OpenAIRE |
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