Ubiquitin-specific protease 25 improves myocardial ischemia–reperfusion injury by deubiquitinating NLRP3 and negatively regulating NLRP3 inflammasome activity in cardiomyocytes
Bozhi Ye , Diyun Xu , Lingfeng Zhong , Yi Wang , Wei Wang , Haowen Xu , Xue Han , Julian Min , Gaojun Wu , Wenhai Huang , Guang Liang
Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (2) : e70243
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. |
cardiomyocyte,myocardial ischemia–reperfusion injury / NLRP3 / pyroptosis / ubiquitin-specific protease 25
2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
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