ArticleAmerican journal of physiology. Renal physiology2015
Pharmacological inhibition of soluble epoxide hydrolase prevents renal interstitial fibrogenesis in obstructive nephropathy.
Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 65 citations in OpenAlex.
- Experimental Characterization Combined with Computational Network Analysis of Metabolites Associated with Chrysanthemum morifolium-derived exosome-like Nanoparticles in Predicting Potential AKI-relevant Targets.Cell biochemistry and biophysics · 2026Article
- Alterations in mitochondria and cellular senescence in aged sEH null female kidneys.GeroScience · 2026Article
- Soluble Epoxide Hydrolase Inhibitors Improve Cornea Alkali Wound Healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-β signaling.iScience · 2024Article
- Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis.Biomolecules & therapeutics · 2024Review
- Regulation of soluble epoxide hydrolase in renal-associated diseases: insights from potential mechanisms to clinical researches.Frontiers in endocrinology · 2024Review
- Salt-sensitive hypertension after reversal of unilateral ureteral obstruction.Biochemical pharmacology · 2023Article
- Epoxyeicosatrienoic acid administration or soluble epoxide hydrolase inhibition attenuates renal fibrogenesis in obstructive nephropathy.American journal of physiology. Renal physiology · 2023Article
- Dual soluble epoxide hydrolase inhibitor - farnesoid X receptor agonist interventional treatment attenuates renal inflammation and fibrosis.Frontiers in immunology · 2023Article
- Cardiomyocyte-specific disruption of soluble epoxide hydrolase limits inflammation to preserve cardiac function.American journal of physiology. Heart and circulatory physiology · 2022Article
- Epoxyeicosatrienoic Acids Inhibit the Activation of Murine Fibroblasts by Blocking the TGF-Oxidative medicine and cellular longevity · 2022Article
- Orally active epoxyeicosatrienoic acid analogs in hypertension and renal injury.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Multitarget molecule, PTUPB, to treat diabetic nephropathy in rats.British journal of pharmacology · 2021Article
- Multi-Target Drugs for Kidney Diseases.Kidney360 · 2021Article
- Epoxyeicosatrienoic Acids and Fibrosis: Recent Insights for the Novel Therapeutic Strategies.International journal of molecular sciences · 2021Review
- Role of Arachidonic Acid and Its Metabolites in the Biological and Clinical Manifestations of Idiopathic Nephrotic Syndrome.International journal of molecular sciences · 2021Review
- Inhibition of the Soluble Epoxide Hydrolase as an Analgesic Strategy: A Review of Preclinical Evidence.Journal of pain research · 2021Review
- Pharmacological inhibition of soluble epoxide hydrolase attenuates chronic experimental autoimmune encephalomyelitis by modulating inflammatory and anti-inflammatory pathways in an inflammasome-dependent and -independent manner.Inflammopharmacology · 2020Article
- Epoxy Fatty Acids: From Salt Regulation to Kidney and Cardiovascular Therapeutics: 2019 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2020Article
- THE EFFECT OF COMPOUND DM509 ON KIDNEY FIBROSIS IN THE CONDITIONS OF THE EXPERIMENTAL MODEL.Visnyk Kyivs'koho natsional'noho universytetu imeni Tarasa Shevchenka. Biolohiia · 2020Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Treating chronic kidney disease (CKD) has been challenging because of its pathogenic complexity. Epoxyeicosatrienoic acids (EETs) are cytochrome P-450-dependent derivatives of arachidonic acid with antihypertensive, anti-inflammatory, and profibrinolytic functions. We recently reported that genetic ablation of soluble epoxide hydrolase (sEH), an enzyme that converts EETs to less active dihydroxyeicosatrienoic acids, prevents renal tubulointerstitial fibrosis and inflammation in experimental mouse models of CKD. Here, we tested the hypothesis that pharmacological inhibition of sEH after unilateral ureteral obstruction (UUO) would attenuate tubulointerstitial fibrosis and inflammation in mouse kidneys and may provide a novel approach to manage the progression of CKD. Inhibition of sEH enhanced levels of EET regioisomers and abolished tubulointerstitial fibrosis, as demonstrated by reduced collagen deposition and myofibroblast formation after UUO. The inflammatory response was also attenuated, as demonstrated by decreased influx of neutrophils and macrophages and decreased expression of inflammatory cytokines keratinocyte chemoattractant, macrophage inflammatory protein-2, monocyte chemotactic protein-1, TNF-α, and ICAM-1 in kidneys after UUO. UUO upregulated transforming growth factor-β1/Smad3 signaling and induced NF-κB activation, oxidative stress, tubular injury, and apoptosis; in contrast, it downregulated antifibrotic factors, including peroxisome proliferator-activated receptor (PPAR) isoforms, especially PPAR-γ. sEH inhibition mitigated the aforementioned malevolent effects in UUO kidneys. These data demonstrate that pharmacological inhibition of sEH promotes anti-inflammatory and fibroprotective effects in UUO kidneys by preventing tubular injury, downregulation of NF-κB, transforming growth factor-β1/Smad3, and inflammatory signaling pathways, and activation of PPAR isoforms. Our data suggest the potential use of sEH inhibitors in treating fibrogenesis in the UUO model of CKD.
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