ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2011
Deletion of soluble epoxide hydrolase gene improves renal endothelial function and reduces renal inflammation and injury in streptozotocin-induced type 1 diabetes.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
- Alterations in mitochondria and cellular senescence in aged sEH null female kidneys.GeroScience · 2026Article
- Intersecting Pathways of Inflammation, Oxidative Stress, and Atherogenesis in the Evaluation of CKD: Emerging Biomarkers PCSK9, EPHX2, AOPPs, and TBARSs.Life (Basel, Switzerland) · 2025Review
- Structure-Based Design of PROTACS for the Degradation of Soluble Epoxide Hydrolase.Journal of medicinal chemistry · 2025Article
- Soluble Epoxide Hydrolase Inhibition Attenuates Proteinuria by Alleviating Renal Inflammation and Podocyte Injuries in Adriamycin-Induced Nephropathy.International journal of molecular sciences · 2024Article
- Regulation of soluble epoxide hydrolase in renal-associated diseases: insights from potential mechanisms to clinical researches.Frontiers in endocrinology · 2024Review
- Hyperhomocysteinemia dysregulates plasma levels of polyunsaturated fatty acids-derived eicosanoids.Life research · 2022Article
- Subproteomic profiling from renal cortices in OLETF rats reveals mutations of multiple novel genes in diabetic nephropathy.Genes & genomics · 2022Article
- Discovery of Soluble Epoxide Hydrolase Inhibitors from Chemical Synthesis and Natural Products.Journal of medicinal chemistry · 2021Review
- Dual sEH/COX-2 Inhibition Using PTUPB-A Promising Approach to Antiangiogenesis-Induced Nephrotoxicity.Frontiers in pharmacology · 2021Article
- The Multifaceted Role of Epoxide Hydrolases in Human Health and Disease.International journal of molecular sciences · 2020Review
- Inhibition of soluble epoxide hydrolase attenuates renal tubular mitochondrial dysfunction and ER stress by restoring autophagic flux in diabetic nephropathy.Cell death & disease · 2020Article
- Mechanism of Chronic Kidney Disease Progression and Novel Biomarkers: A Metabolomic Analysis of Experimental Glomerulonephritis.Metabolites · 2020Article
- Ephx2-gene deletion affects acetylcholine-induced relaxation in angiotensin-II infused mice: role of nitric oxide and CYP-epoxygenases.Molecular and cellular biochemistry · 2020Article
- The Human Genetic Variants CYP2J2 rs2280275 and EPHX2 rs751141 and Risk of Diabetic Nephropathy in Egyptian Type 2 Diabetic Patients.The application of clinical genetics · 2020Article
- A synthetic epoxyeicosatrienoic acid analogue prevents the initiation of ischemic acute kidney injury.Acta physiologica (Oxford, England) · 2019Article
- Prospective for cytochrome P450 epoxygenase cardiovascular and renal therapeutics.Pharmacology & therapeutics · 2018Review
- Role of the cytochrome P-450/ epoxyeicosatrienoic acids pathway in the pathogenesis of renal dysfunction in cirrhosis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2018Article
- Inhibition of Soluble Epoxide Hydrolase 2 Ameliorates Diabetic Keratopathy and Impaired Wound Healing in Mouse Corneas.Diabetes · 2018Article
- Deletion of soluble epoxide hydrolase attenuates mice Hyperoxic acute lung injury.BMC anesthesiology · 2018Article
- Association ofJournal of diabetes research · 2018Article
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Studies suggest that soluble epoxide hydrolase (sEH) inhibition reduces end-organ damage in cardiovascular diseases. We hypothesize that sEH gene (Ephx2) knockout (KO) improves endothelial function and reduces renal injury in streptozotocin-induced diabetes. After 6 wk of diabetes, afferent arteriolar relaxation to acetylcholine was impaired in diabetic wild-type (WT) mice, as the maximum relaxation was 72% of baseline diameter in the WT but only 31% in the diabetic mice. Ephx2 KO improved afferent arteriolar relaxation to acetylcholine in diabetes as maximum relaxation was 58%. Urinary monocyte chemoattractant protein-1 (MCP-1) excretion significantly increased in diabetic WT mice compared with control (868 ± 195 vs. 31.5 ± 7 pg/day), and this increase was attenuated in diabetic Ephx2 KO mice (420 ± 98 pg/day). The renal phospho-IKK-to-IKK ratio and nuclear factor-κB were significantly decreased, and hemeoxygenase-1 (HO-1) expression increased in diabetic Ephx2 KO compared with diabetic WT mice. Renal NADPH oxidase and urinary thiobarbituric acid reactive substances excretion were reduced in diabetic Ephx2 KO compared with diabetic WT mice. Albuminuria was also elevated in diabetic WT mice compared with control (170 ± 43 vs. 37 ± 13 μg/day), and Ephx2 KO reduced this elevation (50 ± 15 μg/day). Inhibition of sEH using trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (tAUCB) also reduced renal inflammation and injury in diabetic WT mice. Furthermore, inhibition of HO with stannous mesoporphyrin negated the reno-protective effects of tAUCB or Ephx2 KO during diabetes. These data demonstrate that Ephx2 KO improves endothelial function and reduces renal injury during diabetes. Additionally, our data also suggest that activation of HO-1 contributes to improved renal injury in diabetic Ephx2 KO mice.
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