ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-induced Liver Injury Through miR-122/BCL2A1 Signaling

作     者：Shanshou Liu Jiangang Xie Chujun Duan Xiaojun Zhao Zhusheng Feng Zheng Dai Xu Luo Yu Li Minghe Yang Ran Zhuang Junjie Li Wen Yin 

作者机构：Emergency DepartmentXijing HospitalFourth Military Medical UniversityXi’anShaanxiChina Emergency DepartmentTangdu HospitalFourth Military Medical UniversityXi’anShaanxiChina Third Student BrigadeSchool of Basic Medical ScienceFourth Military Medical UniversityXi’anShaanxiChina Department of ImmunologyFourth Military Medical UniversityXi’anShaanxiChina 

出 版 物：《Journal of Clinical and Translational Hepatology》 (临床与转化肝病杂志（英文版）)

年 卷 期：2024年第12卷第2期

页      面：134-150页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the Basic research program of Natural Science in Shaanxi Province(No.2020JQ-466) Key research and development program of Shaanxi Province(No.2021SF-014) University Supporting Grant(No.2020rcfczr) Basic research project of the Logistics Support Department of the Chinese Military Commission(No.BWS21J002) National Natural Science Foundation of China(No.81871587) 

主　　题：Sepsis Macrophage ADAR1 microRNA122 BCL2A1 Apoptosis 

摘      要：apoptosis plays regulatory roles in the pathogenesis of immunosuppression and organ *** previously reported that adenosine deaminases acting on RNA-1(ADAR1)reduced intestinal and splenic inflammatory damage during ***,the roles and mechanism of ADAR1 in sepsis-induced liver injury remain ***:We performed transcriptome and single-cell RNA sequencing of peripheral blood mononuclear cells(PBMCs)from patients with sepsis to investigate the effects of ADAR1 on immune cell *** also employed a cecal ligation and puncture(CLP)sepsis mouse model to evaluate the roles of ADAR1 in sepsisinduced liver ***,we treated murine RAW 264.7 macrophages with lipopolysaccharide to explore the underlying ADAR1-mediated mechanisms in ***:PBMCs from patients with sepsis had obvious apoptotic morphological ***-cell RNA sequencing indicated that apoptosis-related pathways were enriched in monocytes,with significantly elevated ADAR1 and BCL2A1 expression in severe ***-induced septic mice had aggravated liver injury and Kupffer cell apoptosis that were largely alleviated by ADAR1 ***1 directly bound to premiR-122 to modulate miR-122 ***-122 was an upstream regulator of ***,ADAR1 also reduced macrophage apoptosis in mice with CLP-induced sepsis through the miR-122/BCL2A1 signaling pathway and protected against sepsis-induced liver ***:The findings show that ADAR1 alleviates macrophage apoptosis and sepsis-induced liver damage through the miR-122/BCL2A1 signaling *** study provides novel insights into the development of therapeutic interventions in sepsis.