ArticleFrontiers in pharmacology2017
Epoxyeicosatrienoic Acid Analog Decreases Renal Fibrosis by Reducing Epithelial-to-Mesenchymal Transition.
Article in Frontiers in pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Multiple Reaction Monitoring (MRM)-Based Targeted Kidney Metabolite Profiling of a Mouse Model of Hyperuricemia.Metabolites · 2026Article
- Kidney Injury by Unilateral Ureteral Obstruction in Mice Lacks Sex Differences.Kidney & blood pressure research · 2024Article
- 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
- Inactivation of fatty acid amide hydrolase protects against ischemic reperfusion injury-induced renal fibrogenesis.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Orally active epoxyeicosatrienoic acid analogs in hypertension and renal injury.Advances in pharmacology (San Diego, Calif.) · 2022Article
- COX-2/sEH Dual Inhibitor PTUPB Attenuates Epithelial-Mesenchymal Transformation of Alveolar Epithelial CellsOxidative medicine and cellular longevity · 2022Article
- Epoxyeicosatrienoic Acids and Fibrosis: Recent Insights for the Novel Therapeutic Strategies.International journal of molecular sciences · 2021Review
- Kidney-Targeted Epoxyeicosatrienoic Acid Analog, EET-F01, Reduces Inflammation, Oxidative Stress, and Cisplatin-Induced Nephrotoxicity.International journal of molecular sciences · 2021Article
- Epoxy Fatty Acids: From Salt Regulation to Kidney and Cardiovascular Therapeutics: 2019 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2020Article
- COX-2/sEH dual inhibitor PTUPB alleviates bleomycin-induced pulmonary fibrosis in mice via inhibiting senescence.The FEBS journal · 2020Article
- Dissecting Efficacy and Metabolic Characteristic Mechanism ofFrontiers in pharmacology · 2020Article
- Design, synthesis and evaluation of novel 3,5-disubstituted benzamide derivatives as allosteric glucokinase activators.BMC chemistry · 2019Article
- In-silico design, synthesis, ADMET studies and biological evaluation of novel derivatives of Chlorogenic acid against Urease protein andBMC chemistry · 2019Article
- Lead optimization for promising monoamine oxidase inhibitor from eugenol for the treatment of neurological disorder: synthesis and in silico based study.BMC chemistry · 2019Article
- A dual farnesoid X receptor/soluble epoxide hydrolase modulator treats non-alcoholic steatohepatitis in mice.Biochemical pharmacology · 2019Article
- Identification of the Perturbed Metabolic Pathways Associating With Renal Fibrosis and Evaluating Metabolome Changes of Pretreatment With Astragalus polysaccharide Through Liquid Chromatography Quadrupole Time-Of-Flight Mass Spectrometry.Frontiers in pharmacology · 2019Article
- Epoxyeicosatrienoic Acid Analog EET-A Blunts Development of Lupus Nephritis in Mice.Frontiers in pharmacology · 2019Article
- Epoxyeicosatrienoic Acid-Based Therapy Attenuates the Progression of Postischemic Heart Failure in Normotensive Sprague-Dawley but Not in HypertensiveFrontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Renal fibrosis, which is a critical pathophysiological event in chronic kidney diseases, is associated with renal epithelial-to-mesenchymal transition (EMT). Epoxyeicosatrienoic acids (EETs) are Cyp epoxygenase arachidonic acid metabolites that demonstrate biological actions that result in kidney protection. Herein, we investigated the ability of 14,15-EET and its synthetic analog, EET-A, to reduce kidney fibrosis induced by unilateral ureter obstruction (UUO). C57/BL6 male mice underwent sham or UUO surgical procedures and were treated with 14,15-EET or EET-A in osmotic pump (i.p.) for 10 days following UUO surgery. UUO mice demonstrated renal fibrosis with an 80% higher kidney-collagen positive area and 70% higher α-smooth muscle actin (SMA) positive renal areas compared to the sham group. As a measure of collagen content, kidney hydroxyproline content was also higher in UUO (6.4 ± 0.5 μg/10 mg) compared to sham group (2.5 ± 0.1 μg/10 mg). Along with marked renal fibrosis, UUO mice had reduced renal expression of EET producing Cyp epoxygenase enzymes. Endogenous 14,15-EET or EET-A demonstrated anti-fibrotic action in UUO by reducing kidney-collagen positive area (50-60%), hydroxyproline content (50%), and renal α-SMA positive area (85%). In UUO mice, renal expression of EMT inducers, Snail1 and ZEB1 were higher compared to sham group. Accordingly, renal epithelial marker E-cadherin expression was reduced and mesenchymal marker expression was elevated in the UUO compared to sham mice. Interestingly, EET-A reduced EMT in UUO mice by deceasing renal Snail1 and ZEB1 expression. EET-A treatment also opposed the decrease in renal E-cadherin expression and markedly reduced several prominent renal mesenchymal/myofibroblast markers in UUO mice. Overall, our results demonstrate that EET-A is a novel anti-fibrotic agent that reduces renal fibrosis by decreasing renal EMT.
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