ArticleProceedings of the National Academy of Sciences of the United States of America2017
Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney injury involved in GSK3β signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Impaired fatty acid metabolism in AKI: experimental evidence - a narrative review.BMC nephrology · 2026Review
- Inhibition of soluble epoxide hydrolase ameliorates renal injury in IgA nephropathy by restoring epoxyeicosatrienoic acids.iScience · 2026Article
- Plasma oxylipin profiling reveals the step-wise activation of ARA/5-HETE metabolism in diabetic kidney disease.Journal of lipid research · 2026Article
- Targeting CDC42 Protects Mitochondrial Function through KLF2/HIF-1α/PINK1 Signaling in Acute Kidney Injury.International journal of biological sciences · 2026Article
- Sex-Specific Differences in Rat Renal CYP Enzyme Expression and Activity Following Isoproterenol-Induced Injury.European journal of drug metabolism and pharmacokinetics · 2026Article
- Kidney lipid metabolism: impact on pediatric kidney diseases and modulation by early-life nutrition.Pediatric nephrology (Berlin, Germany) · 2025Review
- Epoxy metabolites of linoleic acid promote the development of breast cancer via orchestrating PLEC/NFκB1/CXCL9-mediated tumor growth and metastasis.Cell death & disease · 2024Article
- Metabolomics reveals soluble epoxide hydrolase as a therapeutic target for high-sucrose diet-mediated gut barrier dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition.Frontiers in pharmacology · 2024Review
- Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase attenuated particulate matter 2.5 exposure mediated lung injury.Journal of hazardous materials · 2023Article
- Lipidome modulation by dietary omega-3 polyunsaturated fatty acid supplementation or selective soluble epoxide hydrolase inhibition suppresses rough LPS-accelerated glomerulonephritis in lupus-prone mice.Frontiers in immunology · 2023Article
- Direct targeting of sEH with alisol B alleviated the apoptosis, inflammation, and oxidative stress in cisplatin-induced acute kidney injury.International journal of biological sciences · 2023Article
- High Sensitivity and Wide Linearity LC-MS/MS Method for Oxylipin Quantification in Multiple Biological Samples.Journal of lipid research · 2022Article
- The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms.Prostaglandins & other lipid mediators · 2022Article
- CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators.Molecules (Basel, Switzerland) · 2022Review
- Omega-3 fatty acid epoxides produced by PAF-AH2 in mast cells regulate pulmonary vascular remodeling.Nature communications · 2022Article
- NADJournal of cellular and molecular medicine · 2022Article
- Kurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Inhibition of sEH via stabilizing the level of EETs alleviated Alzheimer's disease through GSK3β signaling pathway.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2021Article
- Downregulation of XBP1 protects kidney against ischemia-reperfusion injury via suppressing HRD1-mediated NRF2 ubiquitylation.Cell death discovery · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Acute kidney injury (AKI) causes severe morbidity and mortality for which new therapeutic strategies are needed. Docosahexaenoic acid (DHA), arachidonic acid (ARA), and their metabolites have various effects in kidney injury, but their molecular mechanisms are largely unknown. Here, we report that 14 (15)-epoxyeicosatrienoic acid [14 (15)-EET] and 19 (20)-epoxydocosapentaenoic acid [19 (20)-EDP], the major epoxide metabolites of ARA and DHA, respectively, have contradictory effects on kidney injury in a murine model of ischemia/reperfusion (I/R)-caused AKI. Specifically, 14 (15)-EET mitigated while 19 (20)-EDP exacerbated I/R kidney injury. Manipulation of the endogenous 19 (20)-EDP or 14 (15)-EET by alteration of their degradation or biosynthesis with selective inhibitors resulted in anticipated effects. These observations are supported by renal histological analysis, plasma levels of creatinine and urea nitrogen, and renal NGAL. The 14 (15)-EET significantly reversed the I/R-caused reduction in glycogen synthase kinase 3β (GSK3β) phosphorylation in murine kidney, dose-dependently inhibited the hypoxia/reoxygenation (H/R)-caused apoptosis of murine renal tubular epithelial cells (mRTECs), and reversed the H/R-caused reduction in GSK3β phosphorylation in mRTECs. In contrast, 19 (20)-EDP dose-dependently promoted H/R-caused apoptosis and worsened the reduction in GSK3β phosphorylation in mRTECs. In addition, 19 (20)-EDP was more metabolically stable than 14 (15)-EET in vivo and in vitro. Overall, these epoxide metabolites of ARA and DHA function conversely in I/R-AKI, possibly through their largely different metabolic stability and their opposite effects in modulation of H/R-caused RTEC apoptosis and GSK3β phosphorylation. This study provides AKI patients with promising therapeutic strategies and clinical cautions.
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