Matr3 reshapes m6A modification complex to alleviate macrophage inflammation during atherosclerosis

Copyright © 2022 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 245(2022) vom: 10. Dez., Seite 109176
1. Verfasser: Sun, Zewei (VerfasserIn)
Weitere Verfasser: Chen, Wenjing, Wang, Zhen, Wang, Shuai, Zan, Jie, Zheng, Liangrong, Zhao, Wenting
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2022
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Atherosclerosis Macrophage Matrin-3 Mettl14 N6-methyladenosine (m6A) modification Methyltransferases EC 2.1.1.- RNA-Binding Proteins mehr... METTL3 protein, human EC 2.1.1.62 MATR3 protein, human Nuclear Matrix-Associated Proteins
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520 |a Atherosclerosis, characterized as the chronic inflammation of the arterial wall, is one of the leading causes of coronary artery disease (CAD), and macrophages are found to play essential roles in the initiation and progression of inflammation in atherosclerosis. N6-methyladenosine (m6A) modification, as the most abundant epi-transcriptomic modification in mRNA, is found to mediate the atherogenic inflammatory cascades in vascular endothelium. The detailed molecular mechanism of m6A methylation regulating inflammatory response during atherosclerosis is still not fully known. In this study, we find oxidized low-density lipoprotein (oxLDL) stimulation increases methyltransferases Mettl3 and Mettl14 expressions in macrophages, whereas the total m6A modification level in macrophages decreases under oxLDL stimulation. Matrin-3 (Matr3), an RNA binding protein, is identified to play a suppressive role on oxLDL-mediated macrophage inflammatory responses through inhibiting activation of pro-inflammatory signaling, mitogen-activated protein kinase (Mapk) by m6A-mediated mRNA decay via regulating the formation of Mettl3-Mettl14 complex. Moreover, we find that Matr3 expression decreases in the oxLDL-stimulated macrophages, and the peripheral blood-derived monocytes from patients with CAD, and overexpression of Matr3 significantly alleviates atherosclerosis development in vivo. Our study for the first time clarifies the role of Matr3 on macrophage inflammatory responses during atherosclerotic development, and supplies deep understanding on the relationship of m6A modification and inflammatory responses in atherosclerosis 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Atherosclerosis 
650 4 |a Macrophage 
650 4 |a Matrin-3 
650 4 |a Mettl14 
650 4 |a N6-methyladenosine (m6A) modification 
650 7 |a Methyltransferases  |2 NLM 
650 7 |a EC 2.1.1.-  |2 NLM 
650 7 |a RNA-Binding Proteins  |2 NLM 
650 7 |a METTL3 protein, human  |2 NLM 
650 7 |a EC 2.1.1.62  |2 NLM 
650 7 |a MATR3 protein, human  |2 NLM 
650 7 |a Nuclear Matrix-Associated Proteins  |2 NLM 
700 1 |a Chen, Wenjing  |e verfasserin  |4 aut 
700 1 |a Wang, Zhen  |e verfasserin  |4 aut 
700 1 |a Wang, Shuai  |e verfasserin  |4 aut 
700 1 |a Zan, Jie  |e verfasserin  |4 aut 
700 1 |a Zheng, Liangrong  |e verfasserin  |4 aut 
700 1 |a Zhao, Wenting  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Clinical immunology (Orlando, Fla.)  |d 1999  |g 245(2022) vom: 10. Dez., Seite 109176  |w (DE-627)NLM098196855  |x 1521-7035  |7 nnns 
773 1 8 |g volume:245  |g year:2022  |g day:10  |g month:12  |g pages:109176 
856 4 0 |u http://dx.doi.org/10.1016/j.clim.2022.109176  |3 Volltext 
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