ArticleClinical and translational medicine2025
Ubiquitin-specific protease 25 improves myocardial ischemia-reperfusion injury by deubiquitinating NLRP3 and negatively regulating NLRP3 inflammasome activity in cardiomyocytes.
Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed.
- Ubiquitin-Related Proteostatic Programs in Cycling Fibroblast-Lineage Remodeling After Myocardial Ischemic Injury: A Hypothesis Informed by Single-Cell and Spatial Transcriptomics.International journal of molecular sciences · 2026Review
- Rutin as a Potential Therapeutic Agent for Multi-Organ Ischemia-Reperfusion Injury: From Multidimensional Mechanisms to Clinical Translation.Molecules (Basel, Switzerland) · 2026Review
- USP25 inhibition ameliorates Parkinson's disease by restoring mitophagy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Delta opioid peptide (D-Ala2, D-Leu5)-enkephalin (DADLE) mitigates myocardial ischemia-reperfusion injury by inhibiting the TRAF6/NF-κB/NLRP3 pathway.Iranian journal of basic medical sciences · 2026Article
- Ubiquitin-specific protease 25: a new regulator for cardiovascular and cerebrovascular diseases.Frontiers in cell and developmental biology · 2026Review
- NLRP3-mediated pyroptosis in cardiovascular disease: from molecular mechanisms to therapeutic targets.Frontiers in pharmacology · 2026Review
- The cardiovascular-immune axis: crosstalk and therapy in atherosclerosis, myocarditis and vasculitis.Frontiers in immunology · 2026Review
- Identification of Pyroptosis-Related Genes and Immune Landscape in Myocardial Ischemia-Reperfusion Injury.Biomedicines · 2025Article
- Identification and validation of USP15 and CUL2 as ubiquitination related biomarker in chronic obstructive pulmonary disease.Hereditas · 2025Article
- Nlrc4 Inflammasome Expression After Acute Myocardial Infarction in Rats.International journal of molecular sciences · 2025Article
- Ubiquitin-specific protease 25 improves myocardial ischemia-reperfusion injury by deubiquitinating NLRP3 and negatively regulating NLRP3 inflammasome activity in cardiomyocytes.Clinical and translational medicine · 2025Article
- Ubiquitination-mediated protein homeostasis in cardiovascular diseases: molecular mechanisms and therapeutic opportunities.American journal of cardiovascular disease · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundMyocardial ischemia/reperfusion injury (MI/RI) restricts the effect of myocardial reperfusion therapy and lacks effective prevention and treatment methods. Deubiquitinating enzymes (DUBs), especially members of the ubiquitin-specific protease (USP) family of DUBs, are key proteins in the ubiquitination modification process and play a vital role in MI/RI. Therefore, we aimed to investigate the role of USP25, as a member of the USP family, in MI/RI and its molecular mechanism.
methodsTranscriptome sequencing was applied to evaluate the differential expression of USP families during hypoxia/reoxygenation (H/R) and validated in human and mouse heart samples and cardiomyocytes by performing quantitative polymerase chain reaction. Wild-type or USP25
resultsWe found that the expression level of USP25 was significantly decreased in I/R-induced mouse heart tissues and primary cardiomyocytes in a time-dependent manner. USP25 deficiency exacerbated MI/RI and aggravated I/R-induced cardiac remodelling in mice. Mechanistically, USP25 directly binds to NLRP3 protein and K63-linkedly deubiquitinates NLRP3 at residue K243 via its active site C178, thus hindering NLRP3-ASC interaction and ASC oligomerization to inhibit NLRP3 activation and pyroptosis in cardiomyocytes. We further showed that the overexpression of USP25 in cardiomyocytes ameliorated MI/RI in mice, whereas this protective effect disappeared when NLRP3 is knocked out.
conclusionsOur study demonstrated that USP25 ameliorates MI/RI by regulating NLRP3 activation and its mediated pyroptosis. This finding extends the protective role of USP25 in cardiovascular disease and provides an experimental basis for future USP25-based drug development for the treatment of MI/RI. KEY POINTS: 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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.