ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Targeting RNA oxidation by ISG20-mediated degradation is a potential therapeutic strategy for acute kidney injury.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- Ribonucleobase Oxidation and Ribonucleases Involved in the Degradation of Oxidized RNA.Biomolecules · 2026Review
- Therapeutic potential of ISG20 in attenuating podocyte injury via inhibition of ferroptosis.Molecular therapy. Nucleic acids · 2026Article
- Integrated Transcriptomic Analysis Identifies Immune Remodeling and Prognostic Signatures in Uveal Melanoma.International journal of genomics · 2026Article
- ISG20 RestrictsMicroorganisms · 2025Article
- ISG20: The multifaceted 'molecular star' in cancer research (Review).Oncology reports · 2025Review
- Novel ribosome biogenesis-related biomarkers and therapeutic targets identified in psoriasis.Scientific reports · 2025Article
- Article
- RNA damage and its implications in genome stability.DNA repair · 2025Review
- S100A8/A9 high-expression macrophages mediate renal tubular epithelial cell damage in acute kidney injury following acute type A aortic dissection surgery.Frontiers in molecular biosciences · 2025Article
- Causal inference of CLEC5A and ISG20 in atherosclerosis: integrating Mendelian randomization and eQTL evidence.Frontiers in immunology · 2025Article
- A Novel Immune-Related Three-Gene Signature and Immune Infiltration Insights in Psoriasis and Chronic Kidney Disease.Clinical, cosmetic and investigational dermatology · 2025Article
- Article
- Oxysterol-binding protein-like 7 deficiency leads to ER stress-mediated apoptosis in podocytes and proteinuria.American journal of physiology. Renal physiology · 2024Article
- A potential novel therapy addressing RNA oxidative damage in AKI.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Interferon-Stimulated Genes: Novel Targets in Renal Pathogenesis.Kidney diseases (Basel, Switzerland)Review
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress plays a central role in the pathophysiology of acute kidney injury (AKI). Although RNA is one of the most vulnerable cell components to oxidative damage, it is unclear whether RNA oxidation is involved in the pathogenesis of AKI. In this study, we found that the level of RNA oxidation was significantly enhanced in kidneys of patients with acute tubular necrosis (ATN) and in the renal tubular epithelial cells (TECs) of mice with AKI, and oxidized RNA overload resulted in TEC injury. We further identified interferon-stimulated gene 20 (ISG20) as a novel regulator of RNA oxidation in AKI. Tubule-specific deficiency of ISG20 significantly aggravated renal injury and RNA oxidation in the ischemia/reperfusion-induced AKI mouse model and ISG20 restricted RNA oxidation in an exoribonuclease activity-dependent manner. Importantly, overexpression of ISG20 protected against oxidized RNA overproduction and renal ischemia/reperfusion injury in mice and ameliorated subsequent protein aggresome accumulation, endoplasmic reticulum stress, and unfolded protein response. Thus, our findings provide direct evidence that RNA oxidation contributes to the pathogenesis of AKI and that ISG20 importantly participates in the degradation of oxidized RNA, suggesting that targeting ISG20-handled RNA oxidation may be an innovative therapeutic strategy for AKI.
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