Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors

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 cel...

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Autores principales:	Lizhi He, Jhih-Hua Jhong, Qi Chen, Kai-Yao Huang, Karin Strittmatter, Johannes Kreuzer, Michael DeRan, Xu Wu, Tzong-Yi Lee, Nikolai Slavov, Wilhelm Haas, Alexander G. Marneros
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	macrophage polarization M2-type polarization M1-type polarization MEK signaling phosphoproteomics retinoic acid signaling Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f157ca1578fa466bb58ec28d74dce0d4
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spelling	oai:doaj.org-article:f157ca1578fa466bb58ec28d74dce0d42021-11-04T04:29:50ZGlobal characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors2211-124710.1016/j.celrep.2021.109955https://doaj.org/article/f157ca1578fa466bb58ec28d74dce0d42021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014327https://doaj.org/toc/2211-1247Summary: 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.Lizhi HeJhih-Hua JhongQi ChenKai-Yao HuangKarin StrittmatterJohannes KreuzerMichael DeRanXu WuTzong-Yi LeeNikolai SlavovWilhelm HaasAlexander G. MarnerosElsevierarticlemacrophage polarizationM2-type polarizationM1-type polarizationMEK signalingphosphoproteomicsretinoic acid signalingBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109955- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	macrophage polarization M2-type polarization M1-type polarization MEK signaling phosphoproteomics retinoic acid signaling Biology (General) QH301-705.5
spellingShingle	macrophage polarization M2-type polarization M1-type polarization MEK signaling phosphoproteomics retinoic acid signaling Biology (General) QH301-705.5 Lizhi He Jhih-Hua Jhong Qi Chen Kai-Yao Huang Karin Strittmatter Johannes Kreuzer Michael DeRan Xu Wu Tzong-Yi Lee Nikolai Slavov Wilhelm Haas Alexander G. Marneros Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors
description	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.
format	article
author	Lizhi He Jhih-Hua Jhong Qi Chen Kai-Yao Huang Karin Strittmatter Johannes Kreuzer Michael DeRan Xu Wu Tzong-Yi Lee Nikolai Slavov Wilhelm Haas Alexander G. Marneros
author_facet	Lizhi He Jhih-Hua Jhong Qi Chen Kai-Yao Huang Karin Strittmatter Johannes Kreuzer Michael DeRan Xu Wu Tzong-Yi Lee Nikolai Slavov Wilhelm Haas Alexander G. Marneros
author_sort	Lizhi He
title	Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors
title_short	Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors
title_full	Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors
title_fullStr	Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors
title_full_unstemmed	Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors
title_sort	global characterization of macrophage polarization mechanisms and identification of m2-type polarization inhibitors
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/f157ca1578fa466bb58ec28d74dce0d4
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Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors

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