Ubiquitin‐specific protease 25 improves myocardial ischemia–reperfusion injury by deubiquitinating NLRP3 and negatively regulating NLRP3 inflammasome activity in cardiomyocytes
The deubiquitinating enzyme USP25 was down-regulated both in myocardial ischemia/reperfusion injury (MI/RI) myocardium tissues. The deficiency of USP25 worsened exacerbated MI/RI in mice, whereas the overexpression of USP25 in cardiomyocytes mitigated this pathological phenotype. USP25 directly interacts with the NLRP3 protein and deubiquitinates it via K63 linkage at residue K243 through its active site C178, thus affecting NLRP3-ASC interaction and ASC oligomerization to inhibit NLRP3 activation and pyroptosis in cardiomyocytes.
Authors
- Haowen Xu
- Bozhi Ye (ORCID: https://orcid.org/0000-0002-8713-0822)
- Wenhai Huang (ORCID: https://orcid.org/0000-0003-1457-7380)
- Gaojun Wu (ORCID: https://orcid.org/0009-0007-7454-6312)
- Lingfeng Zhong (ORCID: https://orcid.org/0009-0002-3938-8826)
- Diyun Xu
- Guang Liang (ORCID: https://orcid.org/0000-0002-8278-849X)
- Xue Han (ORCID: https://orcid.org/0000-0002-2695-9573)
- Yi Wang (ORCID: https://orcid.org/0000-0001-9048-0092)
- Julian Min
- Wei Wang (ORCID: https://orcid.org/0000-0003-1568-222X)
Institutions
- Hangzhou Normal University (CN)
- Wenzhou Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Zhejiang Provincial People's Hospital (CN)
- Hangzhou Medical College (CN)
Publication Details
- Journal
- Clinical and Translational Medicine
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1002/ctm2.70243
- Citations
- 9
- Primary Topic
- Inflammasome and immune disorders
- Type
- article
- Field-Weighted Citation Impact
- 7.25
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Zhejiang Province