GPX4-Regulated Ferroptosis Mediates S100-Induced Experimental Autoimmune Hepatitis Associated with the Nrf2/HO-1 Signaling Pathway

doi:10.1155/2021/6551069

科研成果详情

题名	GPX4-Regulated Ferroptosis Mediates S100-Induced Experimental Autoimmune Hepatitis Associated with the Nrf2/HO-1 Signaling Pathway
作者	Zhu, Lujian 1; Chen, Dazhi 2; Zhu, Yin 1; Pan, Tongtong 1; Xia, Dingchao 1; Cai, Tingchen 1; Lin, Hongwei1; Lin, Jing1; Jin, Xiaozhi1; Wu, Faling1; Yu, Sijie 1; Zhu, Kailu 1; Xu, Lanman1,3; Chen, Yongping1
发表日期	2021-12-20
发表期刊	OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Digital storage Mammals Signaling Autoimmune disease Cyclooxygenase 2 Glutathione peroxidase Heavy chain Heme oxygenase-1 Mice models Nuclear factors Reactive oxygen Related factors Signalling pathways
其他关键词	CELL-DEATH ; IRON ; MECHANISMS ; CANCER ; LIVER ; INACTIVATION ; STRESS ; ROLES ; ACSL4 ; TNF
摘要	Autoimmune hepatitis (AIH) is an inflammatory autoimmune disease of the liver. Oxidative stress triggered by reactive oxygen radicals is a common pathophysiological basis for the pathogenesis of many liver diseases, and ferroptosis is associated with the toxic accumulation of reactive oxygen species. The signaling transduction pathways responsible for iron processing and lipid-peroxidation mechanisms are believed to drive ferroptosis. However, the specific mechanisms regulating ferroptosis remain unclear. The aims of this investigation were to identify the possible effector functions of ferroptosis, based on glutathione peroxidase 4 (GPX4) regulation in an S100-induced autoimmune hepatitis mouse model and hepatocyte injury models. The S100 liver antigen-induced AIH mouse model was used to detect ferroptotic biomarkers using western blotting. Upregulated levels of cyclooxygenase2 (COX2) and Acyl-Coenzyme A synthase long-chain family member 4 (ACSL4) were observed in the S100-induced AIH model group, while levels of GPX4 and ferritin heavy chain 1 (FTH1) were downregulated (P<0.05). The expression profiles of COX2, ACSL4, GPX4, and FTH1 were restored following the administration of ferrostatin-1. In addition, Nrf2 and HO-1 levels in the S100-induced AIH model mice after treatment with ferrostatin-1 were downregulated compared to the nonferrostatin-1-treated S100-induced AIH model mice (P<0.05). Moreover, COX2 and ACSL4 levels were significantly upregulated, with significant FTH1 downregulation, in the AIH model mice when liver-specific GPX4 was silenced using AAV8 constructs. These data indicate that inhibition of ferroptosis significantly ameliorated the influence of AIH on the Nuclear factor E2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling pathway, and that ferroptosis may act as an initiator or intermediate mediator leading to AIH.
资助项目	Wenzhou Science and Technology Bureau major scientific and technological innovation to attack health care projects [ZY2019008]; Wenzhou Science and Technology Bureau basic medical and health science and technology projects [Y20210147]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [LD21H030002]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81770585, 82070593]
出版者	HINDAWI LTD
出版地	LONDON
ISSN	1942-0900
EISSN	1942-0994
卷号	2021 页码:6551069
DOI	10.1155/2021/6551069
页数	16
WOS类目	Cell Biology
WOS研究方向	Cell Biology
WOS记录号	WOS:000739153300001
收录类别	SCIE ; PUBMED ; EI ; SCOPUS
EI入藏号	20220311469047
EI主题词	Oxygen
URL	查看原文
PubMed ID	34966478
PMC记录号	PMC8712167
SCOPUSEID	2-s2.0-85122744008
通讯作者地址	[Xu, Lanman]Department of Infectious Diseases,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases,Wenzhou Key Laboratory of Hepatology,Hepatology Institute of Wenzhou Medical University,Wenzhou,China ; [Chen, Yongping]Department of Infectious Diseases,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases,Wenzhou Key Laboratory of Hepatology,Hepatology Institute of Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Biochemistry;Aging;Cell Biology
引用统计	被引频次：4[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/5436
专题	第一临床医学院（信息与工程学院）、附属第一医院_精准医学中心实验室附属第一医院
通讯作者	Xu, Lanman; Chen, Yongping
作者单位	1.Department of Infectious Diseases,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases,Wenzhou Key Laboratory of Hepatology,Hepatology Institute of Wenzhou Medical University,Wenzhou,China; 2.Department of Gastroenterology,Peking University First Hospital,Beijing,China; 3.Department of Infectious Diseases and Liver Diseases,Ningbo Medical Centre Lihuili Hospital,Affiliated Lihuili Hospital of Ningbo University,Ningbo Institute of Innovation for Combined Medicine and Engineering,Ningbo,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Zhu, Lujian,Chen, Dazhi,Zhu, Yin,et al. GPX4-Regulated Ferroptosis Mediates S100-Induced Experimental Autoimmune Hepatitis Associated with the Nrf2/HO-1 Signaling Pathway[J]. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY,2021,2021:6551069.
APA	Zhu, Lujian., Chen, Dazhi., Zhu, Yin., Pan, Tongtong., Xia, Dingchao., ... & Chen, Yongping. (2021). GPX4-Regulated Ferroptosis Mediates S100-Induced Experimental Autoimmune Hepatitis Associated with the Nrf2/HO-1 Signaling Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2021, 6551069.
MLA	Zhu, Lujian,et al."GPX4-Regulated Ferroptosis Mediates S100-Induced Experimental Autoimmune Hepatitis Associated with the Nrf2/HO-1 Signaling Pathway".OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021(2021):6551069.