RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis
| Autor: | Ning Huangfu, Yong Wang, Shuangshuang Zhang, Xiaomin Chen, Shenghuang Wang, Zhenwei Li, Jingsong Cheng, Wenyuan Zheng, Zhenyu Xu, Ke'ai Cheng, Jianhua Zhu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunoprecipitation Immunology Macrophage polarization 03 medical and health sciences Gene Knockout Techniques Interferon-gamma Mice 0302 clinical medicine Immunology and Allergy Animals STAT1 RNA Messenger Tissue homeostasis Pharmacology Messenger RNA Gene knockdown biology Chemistry Macrophages RNA-Binding Proteins Macrophage Activation Cell biology 030104 developmental biology RAW 264.7 Cells STAT1 Transcription Factor Cell culture 030220 oncology & carcinogenesis STAT protein biology.protein Glycolysis |
| Zdroj: | International immunopharmacology. 83 |
| ISSN: | 1878-1705 |
| Popis: | M1/M2 macrophages polarization play important roles in regulating tissue homeostasis. Recently, RNA-binding motif 4 (RBM4) has been reported to modulate the proliferation and expression of inflammatory factors in HeLa cells. However, whether RBM4 is involved in regulating macrophage polarization and inflammatory factor expression are still unknown. In this study, RAW264.7, a mouse macrophage cell line, were stimulated with interferon γ (IFN-γ) or interleukin-4 (IL-4) to induce M1/M2 macrophages polarization. We found that IFN-γ, but not IL-4, stimulation decreased RBM4 expression in macrophages, and RBM4 overexpression inhibits IFN-γ-induced M1 macrophage polarization. Furthermore, RNA-Sequencing, protein immunoprecipitation accompanied with mass spectrometry, and extracellular acidification rate analysis showed that RBM4 suppresses IFN-γ-induced M1 macrophage polarization though inhibiting glycolysis. Moreover, RBM4 knockdown promoted IFN-γ-induced signal transducer and activator of transcription 1 (STAT1) activation via increasing STAT1 mRNA stability, leading to the increase of glycolysis-related gene transcripts regulated by STAT1. Finally, we find that RBM4 interacts with YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) to degrade m6A modified STAT1 mRNA, thereby regulating glycolysis and M1 macrophage polarization. Collectively, the current study firstly reports that RBM4 regulates M1 macrophages polarization through targeting STAT1-mediated glycolysis and shows that RBM4 is a possible candidate for regulating macrophage M1 polarization and inflammatory responses. |
| Databáze: | OpenAIRE |
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