Evidence map›Paper›PMID 42370198›Full record

ArticleTheranostics2026

Cardiomyocyte-derived USP20 mitigates myocardial ischemia/reperfusion injury through deubiquitinating GRP78.

Zhenfeng Cheng, Lingfeng Zhong, Miaomiao Ying, Ziyi Huang, Zexin Yang, Wenli Zhang, Zhouqing Huang, Naijin Zhang, Xudong Chen, Xiaoxi Fan and 7 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Theranostics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Zhenfeng ChengHuzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou, Zhejiang, 313000, China.
Lingfeng ZhongThe Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Miaomiao YingDepartment of Pathology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Ziyi HuangThe Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Zexin YangDepartment of Emergency, The First Affiliated Hospital of Wenzhou Medical University, The Key Laboratory of Emergency and Disaster Medicine of Wenzhou, Wenzhou, Zhejiang, 325000, China.
Wenli ZhangDepartment of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 200000, Shanghai, China.
Zhouqing HuangThe Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Naijin ZhangDepartment of Cardiology, First Hospital of China Medical University, Shenyang City, 110000, China.
Xudong ChenDepartment of Cardiology, Ningbo Hangzhou Bay Hospital, Ningbo, Zhejiang, 315000, China.
Xiaoxi FanThe Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Yucong ZhangThe Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Ruihan ZhengThe Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Keke YeThe Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Shuang LinDepartment of Cardiology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, 315000, China.
Weijian HuangThe Key Laboratory of Cardiovascular Disease of Wenzhou, Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Guangju ZhaoDepartment of Emergency, The First Affiliated Hospital of Wenzhou Medical University, The Key Laboratory of Emergency and Disaster Medicine of Wenzhou, Wenzhou, Zhejiang, 325000, China.
Shanshan DaiDepartment of Emergency, The First Affiliated Hospital of Wenzhou Medical University, The Key Laboratory of Emergency and Disaster Medicine of Wenzhou, Wenzhou, Zhejiang, 325000, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Myocardial ischemia/reperfusion (I/R) injury remains a major clinical challenge characterized by cardiomyocyte loss and adverse remodeling after reperfusion. Ubiquitin-Specific Peptidase 20 (USP20), a deubiquitinase involved in cellular stress responses, has not been fully characterized in the ischemic heart. This study aimed to investigate the function and mechanism of cardiomyocyte-derived USP20 in myocardial I/R injury. Methods: Myocardial I/R models and hypoxia/reoxygenation (H/R)-treated cardiomyocytes were used to evaluate USP20 expression and function. Single-cell transcriptomic analysis, cardiomyocyte-specific USP20 knockout, and USP20 overexpression models were applied. Co-immunoprecipitation, LC-MS/MS, ubiquitination assays, site-directed mutagenesis, and rescue experiments were performed to define the underlying mechanism. Results: USP20 expression was markedly decreased in I/R-injured mouse hearts and H/R-treated cardiomyocytes, and USP20 was predominantly localized in cardiomyocytes. Cardiomyocyte-specific USP20 deletion aggravated myocardial injury, adverse cardiac remodeling, and cardiac dysfunction after I/R, whereas USP20 overexpression conferred significant cardioprotection. Mechanistically, USP20 directly interacted with glucose-regulated protein 78 (GRP78) and removed K63-linked polyubiquitin chains from GRP78 at K602 through its C154 active site. This deubiquitination activated GRP78, promoted adaptive endoplasmic reticulum stress responses, and reduced myocardial injury. Conclusions: These findings identify a previously unrecognized USP20-GRP78 regulatory axis that regulates endoplasmic reticulum stress responses and limits myocardial damage during I/R. USP20 may represent a potential therapeutic target for myocardial I/R injury.

Indexed as

Heat-Shock ProteinsMyocardial Reperfusion InjuryMyocytes, CardiacUbiquitin ThiolesteraseAnimalsDisease Models, AnimalEndoplasmic Reticulum Chaperone BiPMaleMiceMice, Inbred C57BLMice, KnockoutUbiquitinationEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHspa5 protein, mouseUbiquitin Thiolesterasecardiomyocytedeubiquitinating enzymeglucose-regulated protein 78myocardial ischemia/reperfusion injuryubiquitin-specific peptidase 20

Identifiers

PMID42370198
PMCPMC13295839

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.