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FGL2-MCOLN3-Autophagy Axis-Triggered Neutrophil Extracellular Traps Exacerbate Liver Injury in Fulminant Viral Hepatitis

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收录情况： ◇ SCIE

作者：
Li Xitang[1,2,3] * ; Gao Qiang[1,2,3] ; Wu Wenhui[1,2,3] ; Hai Suping[1,2,3] ; Hu Junjian[1,2,3] ; You Jie[1,2,3] ; Huang Da[1,2,3] ; Wang Hongwu[1,2,3] ; Wu Di[1,2,3] ; Han Meifang[1,2,3] ; Xi Dong[1,2,3] ; Yan Weiming[1,2,3] ; Chen Tao[1,2,3] ; Luo Xiaoping[4] ; Ning Qin[1,2,3] ; Wang Xiaojing[1,2,3,*1] ;
单位： [1]Department and Institute of Infectious Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [2]National Medical Center for Major Public Health Events, Wuhan, China [3]State Key Laboratory for Zoonotic Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China. [4]Department and Institute of Pediatrics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China
出处：
DOI： 10.1016/j.jcmgh.2022.07.014
ISSN：

关键词： Neutrophil Extracellular Traps Fibrinogen-Like Protein 2 Fulminant Viral Hepatitis Mucolipin 3 Autophagy

摘要：
Fulminant viral hepatitis (FVH) is a life-threatening disease, but its pathogenesis is not fully understood. Neutrophil extracellular traps (NETs) were an unrecognized link between inflammation and coagulation, which are 2 main features of FVH. Here, we investigated the role and mechanism of NETs in the pathogenesis of FVH.A mouse model of FVH was established by murine hepatitis virus strain-3 infection. Liver leukocytes of infected or uninfected mice were used for single-cell RNA sequencing and whole-transcriptome sequencing. NETs depletion was achieved using DNase1. Acetaminophen was used to establish a mouse model of non-virus-caused acute liver failure. Clinically, NETs-related markers in liver, plasma, and peripheral neutrophils were assessed in patients with hepatitis B virus (HBV)-related acute liver injury.Increased hepatic NETs formation was observed in murine hepatitis virus strain-3-infected mice, but not in acetaminophen-treated mice. NETs depletion improved the liver damage and survival rate in FVH by inhibiting hepatic fibrin deposition and inflammation. An adoptive transfer experiment showed that neutrophil-specific fibrinogen-like protein 2 (FGL2) promoted NETs formation. FGL2 was found to directly interact with mucolipin 3, which regulated calcium influx and initiated autophagy, leading to NETs formation. Clinically, increased plasma NETs level was associated with coagulation dysfunction in patients with HBV acute liver injury. Colocalization of FGL2, NETs, and fibrin in liver was observed in these patients.NETs aggravated liver injury in FVH by promoting fibrin deposition and inflammation. NETs formation was regulated by the FGL2-mucolipin 3-autophagy axis. Targeting NETs may provide a new strategy for the treatment of FVH.Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

基金：
National Key Research and Development Program of China (2021YFC2600200), the National Natural Science Foundation of China (81974075), the National Youth Talent Support Program (0106540082), Wuhan Science and Technology Bureau (2020020601012236), Natural Science Foundation of Hubei Province (2020CFB767), and Youth Science Foundation of Tongji Hospital (2020YQ014).
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外文
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中科院(CAS)分区：
出版当年[2021]版：
大类 | 1 区 医学
小类 | 2 区 胃肠肝病学
最新[2025]版：
大类 | 1 区 医学
小类 | 2 区 胃肠肝病学
JCR分区：
出版当年[2020]版：
Q1 GASTROENTEROLOGY & HEPATOLOGY
最新[2023]版：
Q1 GASTROENTEROLOGY & HEPATOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者单位： [1]Department and Institute of Infectious Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [2]National Medical Center for Major Public Health Events, Wuhan, China [3]State Key Laboratory for Zoonotic Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China.
通讯作者：
通讯机构： [1]Department and Institute of Infectious Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China [2]National Medical Center for Major Public Health Events, Wuhan, China [3]State Key Laboratory for Zoonotic Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,China. [*1]Department and Institute of Infectious Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Wuhan 430030,Hubei,China.
推荐引用方式(GB/T 7714)：
Li Xitang,Gao Qiang,Wu Wenhui,et al.FGL2-MCOLN3-Autophagy Axis-Triggered Neutrophil Extracellular Traps Exacerbate Liver Injury in Fulminant Viral Hepatitis[J].CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY.2022,14(5):1077-1101.doi:10.1016/j.jcmgh.2022.07.014.
APA：
Li Xitang,Gao Qiang,Wu Wenhui,Hai Suping,Hu Junjian...&Wang Xiaojing.(2022).FGL2-MCOLN3-Autophagy Axis-Triggered Neutrophil Extracellular Traps Exacerbate Liver Injury in Fulminant Viral Hepatitis.CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY,14,(5)
MLA：
Li Xitang,et al."FGL2-MCOLN3-Autophagy Axis-Triggered Neutrophil Extracellular Traps Exacerbate Liver Injury in Fulminant Viral Hepatitis".CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY 14..5(2022):1077-1101

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