ArticleLife sciences2023
TRIM21 ubiquitylates GPX4 and promotes ferroptosis to aggravate ischemia/reperfusion-induced acute kidney injury.
Article in Life sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 70 citations in OpenAlex.
- Potential targets and molecular mechanisms of D-pinitol against acute kidney injury based on network pharmacology and experimental validation.Renal failure · 2026Article
- SIRT7-mediated desuccinylation of FOXO4 suppresses ferroptosis to alleviate LPS-induced acute lung injury.Redox biology · 2026Article
- Ferroptosis in prostatitis: pathogenic mechanisms and therapeutic advances.Molecular and cellular biochemistry · 2026Review
- IL-1β/EPAS1-Associated Ferroptotic Stress Impairs Skeletal Stem/Progenitor Cell Function in Inflammation-Associated Fracture Nonunion.Current issues in molecular biology · 2026Article
- Pro-inflammatory cytokine IFN-γ protects against renal fibrosis by promoting E3 ubiquitin ligase Trim21-mediated Loxl2 degradation in tubular epithelial cells.Cell death & disease · 2026Article
- USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers.Redox biology · 2026Article
- OLFM4 mediating ischemia/reperfusion-induced kidney injury by regulating renal tubular epithelial cells ferroptosis via GPX4.Molecular biology reports · 2026Article
- E3 ubiquitin ligase TRIM21-mediated K48-linked ubiquitination of ALDH2 rs671 mutant promotes adverse cardiac remodeling.JCI insight · 2026Article
- Inhibition of Setd7 protects against cardiomyocyte hypertrophy via inhibiting lipid oxidation.Acta pharmacologica Sinica · 2026Article
- Rottlerin triggers dual degradation of SLC7A11 and GPX4 to drive ferroptosis and chemosensitization in hepatocellular carcinoma.Cell death discovery · 2026Article
- Dexmedetomidine alleviates sepsis-associated acute kidney injury by inhibiting renal tubular ferroptosis via JNK/MAPK-LCN2 pathway.European journal of medical research · 2026Article
- Modulating regulated cell death: mechanistic insights into traditional Chinese medicine metabolites for ischemia/reperfusion-induced acute kidney injury.Frontiers in pharmacology · 2026Review
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- Vitexin enhances mitophagy and improves renal ischemia-reperfusion injury by regulating the p38/MAPK pathway.Renal failure · 2025Article
- The Pathogenesis of Chronic Kidney Disease (CKD) and the Preventive and Therapeutic Effects of Natural Products.Current issues in molecular biology · 2025Review
- Coelenterazine alleviates sepsis-associated acute kidney injury by inhibiting ferroptosis via the USP14-NCOA4 pathway.Translational andrology and urology · 2025Article
- TRIM21-Mediated K11-Linked Ubiquitination of ID1 Suppresses Tumorigenesis and Promotes Cuproptosis in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Asperosaponin VI inhibition of DNMT alleviates GPX4 suppression-mediated osteoblast ferroptosis and diabetic osteoporosis.Journal of advanced research · 2025Article
- Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.MedComm · 2025Review
- FXR acts as a therapeutic target for ulcerative colitis via suppressing ferroptosis.Molecular medicine (Cambridge, Mass.) · 2025Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsThis study aims to verify the molecular mechanism that Tripartite motif containing 21 (TRIM21) promotes ubiquitination degradation of glutathione peroxidase 4 (GPX4) by regulating ferroptosis, and to discuss the feasibility of TRIM21 as a new therapeutic target for acute kidney injury (AKI). MATERIALS AND
methodsIschemia-reperfusion (I/R)-AKI model was constructed using Trim21 KEY
findingsIn vivo, TRIM21 is highly expressed in I/R kidney tissues. Loss of TRIM21 alleviated I/R-AKI and improved renal function. The upregulation of GPX4, a key ferroptosis regulator, and the mild mitochondrial damage suggested that loss of TRIM21 had a negative regulation of ferroptosis. In vitro, TRIM21 was highly expressed in H/R models, and overexpression of TRIM21 in HK-2 cells increased ROS production, promoted intracellular iron accumulation, and boosted cellular sensitivity to RSL3 and Erastin. Mechanistically, we confirmed that GPX4 is a substrate of TRIM21 and can be degraded by TRIM21-mediated ubiquitination, suggesting that inhibiting TRIM21 attenuates ferroptosis. A JAK2 inhibitor Fedratinib downregulated TRIM21 expression and reduced damage both in vivo and in vitro, which is correlated with the upregulation of GPX4. SIGNIFICANCE: Our study showed that loss of TRIM21 could alleviate ferroptosis induced by I/R, revealed the mechanism of ubiquitination degradation of GPX4 by TRIM21 and suggested TRIM21 is a potential target for the treatment of AKI.
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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 Socratic graph.