Deubiquitinase USP25 Alleviates Obesity- Induced Cardiac Remodeling and Dysfunction by Downregulating TAK1 and Reducing TAK1-Mediated Inflammation

被引：3

作者：

Ye, Bozhi ^{[1
,2
,3
]}

Chen, Yanghao ^{[1
,2
,3
]}

Chen, Xudong ^{[1
,2
,4
]}

Xu, Diyun ^{[1
,2
,3
]}

Jiang, Yucheng ^{[3
]}

Lin, Wante ^{[1
,2
]}

Fang, Danhong ^{[1
,2
,5
]}

Xu, Jiachen ^{[1
,2
]}

Han, Jibo ^{[3
]}

Han, Xue ^{[3
,6
]}

Long, Xiaohong ^{[3
]}

Wang, Wei ^{[7
,8
]}

Zhou, Hao ^{[1
,2
]}

Wu, Gaojun ^{[1
,2
]}

Liang, Guang ^{[1
,2
,3
,6
]}

机构：

[1] Wenzhou Med Univ, Affiliated Hosp 1, Dept Cardiol, Wenzhou 325035, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Cardiovasc Dis Wenzhou, Wenzhou 325035, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Wenzhou, Zhejiang, Peoples R China

[4] Ningbo Hangzhou Bay Hosp, Dept Cardiol, Ningbo, Zhejiang, Peoples R China

[5] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Cardiol, Hangzhou, Zhejiang, Peoples R China

[6] Hangzhou Med Coll, Sch Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China

[7] Hangzhou Med Coll, Affiliated Yongkang Peoples Hosp 1, Hangzhou, Zhejiang, Peoples R China

[8] Hangzhou Med Coll, Sch Pharm, Hangzhou, Zhejiang, Peoples R China

来源：

JACC-BASIC TO TRANSLATIONAL SCIENCE | 2024年 / 9卷 / 11期

基金：

中国国家自然科学基金;

关键词：

deubiquitinating enzyme; inflammation; obesity cardiomyopathy; TAK1; USP25; CARDIOMYOPATHY; PATHOGENESIS; HYPERTROPHY; CONTRIBUTES; INHIBITION; INJURY;

D O I：

10.1016/j.jacbts.2024.06.001

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Deubiquitinating enzymes play a vital role in cardiovascular diseases. This study found that cardiomyocyte ubiquitin-specific protease 25 (USP25) expression was downregulated both in myocardial tissue of obesity cardiomyopathy and palmitic acid-stimulated cardiomyocytes. USP25 deficiency exacerbated high-fat diet- induced ventricular remodeling in mice, whereas overexpression of USP25 in cardiomyocytes reversed this pathological phenotype. Mechanistically, USP25 directly binds to TAI<1 and P62, and the 178-cysteine of USP25 removes the I<63 ubiquitin chain from P62, which promotes the degradation of TAI<1 through the autophagylysosome pathway, thereby ameliorating obesity-induced ventricular remodeling by reducing inflammation through the TAI<1-MAPI< pathway. This finding identifies USP25 as a potential therapeutic target for obesity cardiomyopathy. (JACC Basic TranslSci. 2024;9:1287-1304) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC- ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：1287 / 1304

页数：18