Journal
CELL REPORTS
Volume 37, Issue 5, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109955
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Funding
- Massachusetts General Hospital
- NIH [NCI U01 CA215798]
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Macrophages undergoing M1 versus M2-type polarization exhibit significant differences in cell metabolism, cellular functions, and signaling pathways, especially in metabolic pathways. Drug screens have identified inhibitors that selectively block M2-type polarization, with MEK signaling being found necessary for M2-type polarization in a proof-of-principle study using comprehensive proteomics and phosphoproteomics datasets.
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-g (PPARg)-induced retinoic acid signaling.
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