Donor graft METTL3 gene transfer ameliorates rat liver transplantation ischemia-reperfusion injury by enhancing HO-1 expression in an m6A-dependent manner

Copyright © 2023 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 251(2023) vom: 06. Juni, Seite 109325
1. Verfasser: Xiang, Song (VerfasserIn)
Weitere Verfasser: Wang, Yihua, Lei, Dengliang, Luo, Yunhai, Peng, Dadi, Zong, Kezhen, Liu, Yanyao, Huang, Zuotian, Mo, Shaojiang, Pu, Xingyu, Zheng, Jinli, Wu, Zhongjun
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't HO-1 Ischemia-reperfusion injury Liver transplantation METTL3 N(6)-methyladenosine RNA 63231-63-0
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245 1 0 |a Donor graft METTL3 gene transfer ameliorates rat liver transplantation ischemia-reperfusion injury by enhancing HO-1 expression in an m6A-dependent manner 
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520 |a Ischemia-reperfusion injury (IRI) is one of the most common complications in liver transplantation. METTL3 regulates inflammation and cellular stress response by modulating RNA m6A modification level. Here, the study aimed to investigate the role and mechanism of METTL3 in IRI after rat orthotopic liver transplantation. The total RNA m6A modification and METTL3 expression level was consistently down-regulated after 6 h or 24 h reperfusion in OLT, which is negatively associated with the hepatic cell apoptosis. Functionally, METTL3 pretreatment in donor significantly inhibited liver grafts apoptosis, improved liver function and depressed the proinflammatory cytokine/chemokine expression. Mechanistically, METTL3 inhibited apoptosis of grafts via upregulating HO-1. Moreover, m6A dot blot and MeRIP-qPCR assay revealed that METTL3 promoted HO-1 expression in an m6A-dependent manner. In vitro, METTL3 alleviated hepatocytes apoptosis by upregulating HO-1 under hypoxia/reoxygenation condition. Taken together, these findings demonstrate that METTL3 ameliorates rat OLT-stressed IRI by inducing HO-1 in an m6A-dependent manner, highlighting a potential target for IRI in liver transplantation 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a HO-1 
650 4 |a Ischemia-reperfusion injury 
650 4 |a Liver transplantation 
650 4 |a METTL3 
650 4 |a N(6)-methyladenosine 
650 7 |a RNA  |2 NLM 
650 7 |a 63231-63-0  |2 NLM 
700 1 |a Wang, Yihua  |e verfasserin  |4 aut 
700 1 |a Lei, Dengliang  |e verfasserin  |4 aut 
700 1 |a Luo, Yunhai  |e verfasserin  |4 aut 
700 1 |a Peng, Dadi  |e verfasserin  |4 aut 
700 1 |a Zong, Kezhen  |e verfasserin  |4 aut 
700 1 |a Liu, Yanyao  |e verfasserin  |4 aut 
700 1 |a Huang, Zuotian  |e verfasserin  |4 aut 
700 1 |a Mo, Shaojiang  |e verfasserin  |4 aut 
700 1 |a Pu, Xingyu  |e verfasserin  |4 aut 
700 1 |a Zheng, Jinli  |e verfasserin  |4 aut 
700 1 |a Wu, Zhongjun  |e verfasserin  |4 aut 
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