USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2

doi:10.1002/advs.202301641

科研成果详情

题名	USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2
作者	Li, Zhongding1,2; Liu, Baohua2; Lambertsen, Kate Lykke 3,4,5; Clausen, Bettina Hjelm 3,4; Zhu, Zhenhu6; Du, Xue6; Xu, Yanqi6; Poulsen, Frantz Rom 4,7; Halle, Bo 4,7; Bonde, Christian 4,7; Chen, Meng 2; Wang, Xue6; Schlüter, Dirk 8; Huang, Jingyong9; Waisman, Ari 10; Song, Weihong1,11; Wang, Xu 1,2,11
发表日期	2023-08-16
发表期刊	ADVANCED SCIENCE 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	cerebral ischemic stroke microglia neuroinflammation ubiquitination USP25
其他关键词	NF-KAPPA-B ; POLYUBIQUITIN CHAINS ; ENZYME A20 ; ACTIVATION ; BINDING ; UBIQUITINATION ; INFLAMMATION ; MECHANISMS ; APOPTOSIS ; RECOVERY
摘要	Cerebral ischemic stroke is a leading cause of morbidity and mortality globally. However, the mechanisms underlying ischemic stroke injury remain poorly understood. Here, it is found that deficiency of the ubiquitin-specific protease USP25 significantly aggravate ischemic stroke injury in mice. USP25 has no impact on neuronal death under hypoxic conditions, but reduced ischemic stroke-induced neuronal loss and neurological deficits by inhibiting microglia-mediated neuroinflammation. Mechanistically, USP25 restricts the activation of NF-& kappa;B and MAPK signaling by regulating TAB2. As a deubiquitinating enzyme, USP25 removeds K63-specific polyubiquitin chains from TAB2. AAV9-mediated TAB2 knockdown ameliorates ischemic stroke injury and abolishes the effect of USP25 deletion. In both mouse and human brains, USP25 is markedly upregulated in microglia in the ischemic penumbra, implying a clinical relevance of USP25 in ischemic stroke. Collectively, USP25 is identified as a critical inhibitor of ischemic stroke injury and this data suggest USP25 may serve as a therapeutic target for ischemic stroke.
资助项目	National Natural Science Foundation of China [81971143, 81900496]
出版者	WILEY
ISSN	2198-3844
EISSN	2198-3844
卷号	10 期号:28
DOI	10.1002/advs.202301641
页数	15
WOS类目	Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
WOS记录号	WOS:001049352900001
收录类别	SCIE ; PUBMED ; EI ; SCOPUS
在线发表日期	2023-08
EI入藏号	20233414584985
EI主题词	Biotechnology
EI分类号	461.8 Biotechnology
URL	查看原文
PubMed ID	37587766
SCOPUSEID	2-s2.0-85168123075
自科自定义期刊分类	T3(B)类
通讯作者地址	[Song, Weihong]Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China ; [Wang, Xu]Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Medicine (miscellaneous);Chemical Engineering (all);Materials Science (all);Biochemistry, Genetics and Molecular Biology (miscellaneous);Engineering (all);Physics and Astronomy (all)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/182274
专题	药学院（分析测试中心）附属第二医院附属第一医院第二临床医学院、附属第二医院、育英儿童医院卓越中心_老年研究院
通讯作者	Wang, Xue; Song, Weihong
作者单位	1.Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine,Vision and Brain Health),School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 2.Department of Neurological Rehabilitation,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,325027,China; 3.Department of Neurobiology Research,Institute of Molecular Medicine,University of Southern Denmark,Odense C,5000,Denmark; 4.BRIDGE – Brain Research – Inter Disciplinary Guided Excellence,Department of Clinical Research,University of Southern Denmark,Odense C,5000,Denmark; 5.Department of Neurology,Odense University Hospital,Odense C,5000,Denmark; 6.School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 7.Department of Neurosurgery,Odense University Hospital,Odense C,5000,Denmark; 8.Institute of Medical Microbiology and Hospital Epidemiology,Hannover Medical School,Hannover,30625,Germany; 9.Department of Vascular Surgery,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325015,China; 10.Institute for Molecular Medicine,Johannes Gutenberg University Mainz,Mainz,55131,Germany; 11.Key Laboratory of Alzheimer's Disease of Zhejiang Province,Institute of Aging,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	药学院（分析测试中心）; 瓯江实验室; 第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
通讯作者单位	药学院（分析测试中心）; 瓯江实验室
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Li, Zhongding,Liu, Baohua,Lambertsen, Kate Lykke,et al. USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2[J]. ADVANCED SCIENCE,2023,10(28).
APA	Li, Zhongding., Liu, Baohua., Lambertsen, Kate Lykke., Clausen, Bettina Hjelm., Zhu, Zhenhu., ... & Wang, Xu. (2023). USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2. ADVANCED SCIENCE, 10(28).
MLA	Li, Zhongding,et al."USP25 Inhibits Neuroinflammatory Responses After Cerebral Ischemic Stroke by Deubiquitinating TAB2".ADVANCED SCIENCE 10.28(2023).