Deubiquitinase OTUD6a drives cardiac inflammation and hypertrophy by deubiquitination of STING

doi:10.1016/j.bbadis.2024.167061

科研成果详情

题名	Deubiquitinase OTUD6a drives cardiac inflammation and hypertrophy by deubiquitination of STING
作者	Fang, Zimin1,2; Han, Jibo 3; Lin, Liming2; Ye, Bozhi1,2; Qu, Xuefeng 4; Zhang, Yu 5; Zhao, Ying 2; Xu, Diyun 1,2; Lin, Wante 1,2; Shen, Sirui 1; Min, Julian 6; Wu, Gaojun1; Huang, Zhouqing1; Liang, Guang1,2,6
发表日期	2024-04
发表期刊	Biochimica et biophysica acta. Molecular basis of disease 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Cardiac hypertrophy Deubiquitination enzyme Inflammation OTU domain-containing protein 6a Stimulator of interferon genes
摘要	Cardiac hypertrophy is a crucial pathological characteristic of hypertensive heart disease and subsequent heart failure. Deubiquitinating enzymes (DUBs) have been found to be involved in the regulation of myocardial hypertrophy. OTU Domain-Containing Protein 6a (OTUD6a) is a recently identified DUB. To date, the potential role of OTUD6a in myocardial hypertrophy has not yet been revealed., {AbstractText=We examined the up-regulated level of OTUD6a in mouse or human hypertrophic heart tissues. Then, transverse aortic constriction (TAC)- or angiotensin II (Ang II)- induced ventricular hypertrophy and dysfunction were significantly attenuated in OTUD6a gene knockout mice (OTUD6a-/-). In mechanism, we identified that the Stimulator of Interferon Genes (STING) is a direct substrate protein of OTUD6a via immunoprecipitation assay and mass spectrometry. OTUD6a maintains STING stability via clearing the K48-linked ubiquitin in cardiomyocytes. Subsequently, OTUD6a regulates the STING-downstream NF-κB signaling activation and inflammatory gene expression both in vivo and in vitro. Inhibition of STING blocked OTUD6a overexpression-induced inflammatory and hypertrophic responses in cardiomyocytes.}, This finding extends our understanding of the detrimental role of OTUD6a in myocardial hypertrophy and identifies STING as a deubiquinating substrate of OTUD6a, indicating that targeting OTUD6a could be a potential strategy for the treatment of cardiac hypertrophy.
资助项目	National Natural Science Foundation of China[81930108,82271347];major scientific and technological innovation project of Wenzhou Science and Technology Bureau[ZY2020016];
出版者	ELSEVIER
ISSN	0925-4439
EISSN	1879-260X
卷号	1870 期号:4
DOI	10.1016/j.bbadis.2024.167061
页数	10
WOS类目	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS记录号	WOS:001187654500001
收录类别	PUBMED ; SCOPUS ; SCIE
在线发表日期	2024-02
URL	查看原文
PubMed ID	38342418
SCOPUSEID	2-s2.0-85185880711
通讯作者地址	[Wu, Gaojun]Department of Cardiology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Liang, Guang]Department of Cardiology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Molecular Medicine;Molecular Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/207603
专题	药学院（分析测试中心）附属第一医院药学院（分析测试中心）_生物有机与药物化学研究中心
通讯作者	Wu, Gaojun; Liang, Guang
作者单位	1.Department of Cardiology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,China; 3.Department of Cardiology,the Second Affiliated Hospital of Jiaxing University,Zhejiang,Jiaxing,China; 4.School of Public Health,Hangzhou Medical College,Zhejiang,Hangzhou,China; 5.Department of Clinical Pharmacy,The First Affiliated Hospital,Zhejiang University School of Medicine,Zhejiang,Hangzhou,China; 6.School of Pharmaceutical Sciences,Hangzhou Medical College,Zhejiang,Hangzhou,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; 药学院（分析测试中心）; 生物有机与药物化学研究中心
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	Fang, Zimin,Han, Jibo,Lin, Liming,et al. Deubiquitinase OTUD6a drives cardiac inflammation and hypertrophy by deubiquitination of STING[J]. Biochimica et biophysica acta. Molecular basis of disease,2024,1870(4).
APA	Fang, Zimin., Han, Jibo., Lin, Liming., Ye, Bozhi., Qu, Xuefeng., ... & Liang, Guang. (2024). Deubiquitinase OTUD6a drives cardiac inflammation and hypertrophy by deubiquitination of STING. Biochimica et biophysica acta. Molecular basis of disease, 1870(4).
MLA	Fang, Zimin,et al."Deubiquitinase OTUD6a drives cardiac inflammation and hypertrophy by deubiquitination of STING".Biochimica et biophysica acta. Molecular basis of disease 1870.4(2024).