ArticleThe Journal of experimental medicine2014
Müller glia cells regulate Notch signaling and retinal angiogenesis via the generation of 19,20-dihydroxydocosapentaenoic acid.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Endothelial AGGF1 promotes retinal angiogenesis by coordinating TNFSF12/FN14 signalling.Nature communications · 2025Article
- A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-β signaling.iScience · 2024Article
- Arachidonic acid metabolism regulates the development of retinopathy of prematurity among preterm infants.Journal of neurochemistry · 2024Article
- Article
- Role of the soluble epoxide hydrolase in keratinocyte proliferation and sensitivity of skin to inflammatory stimuli.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Kindlin-2 controls angiogenesis through modulating Notch1 signaling.Cellular and molecular life sciences : CMLS · 2023Article
- Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease.The Journal of pharmacology and experimental therapeutics · 2023Review
- 11,12-EET Regulates PPAR-γ Expression to Modulate TGF-β-Mediated Macrophage Polarization.Cells · 2023Article
- Decreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization.International journal of molecular sciences · 2022Article
- The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms.Prostaglandins & other lipid mediators · 2022Article
- Role of the soluble epoxide hydrolase in the hair follicle stem cell homeostasis and hair growth.Pflugers Archiv : European journal of physiology · 2022Article
- Redox Regulation of Soluble Epoxide Hydrolase-Implications for Cardiovascular Health and Disease.Cells · 2022Review
- Cyp2c44 epoxygenase-derived epoxyeicosatrienoic acids in vascular smooth muscle cells elicit vasoconstriction of the murine ophthalmic artery.Scientific reports · 2021Article
- The Consequences of Soluble Epoxide Hydrolase Deletion on Tumorigenesis and Metastasis in a Mouse Model of Breast Cancer.International journal of molecular sciences · 2021Article
- Cytochrome P450-epoxygenated fatty acids inhibit Müller glial inflammation.Scientific reports · 2021Article
- The anti-angiogenesis role of FBXW7 in diabetic retinopathy by facilitating the ubiquitination degradation of c-Myc to orchestrate the HDAC2.Journal of cellular and molecular medicine · 2021Article
- Discovery of Soluble Epoxide Hydrolase Inhibitors from Chemical Synthesis and Natural Products.Journal of medicinal chemistry · 2021Review
- Geniposide Attenuates Hyperglycemia-Induced Oxidative Stress and Inflammation by Activating the Nrf2 Signaling Pathway in Experimental Diabetic Retinopathy.Oxidative medicine and cellular longevity · 2021Article
- Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytochrome P450 (CYP) epoxygenases generate bioactive lipid epoxides which can be further metabolized to supposedly less active diols by the soluble epoxide hydrolase (sEH). As the role of epoxides and diols in angiogenesis is unclear, we compared retinal vasculature development in wild-type and sEH(-/-) mice. Deletion of the sEH significantly delayed angiogenesis, tip cell, and filopodia formation, a phenomenon associated with activation of the Notch signaling pathway. In the retina, sEH was localized in Müller glia cells, and Müller cell-specific sEH deletion reproduced the sEH(-/-) retinal phenotype. Lipid profiling revealed that sEH deletion decreased retinal and Müller cell levels of 19,20-dihydroxydocosapentaenoic acid (DHDP), a diol of docosahexenoic acid (DHA). 19,20-DHDP suppressed endothelial Notch signaling in vitro via inhibition of the γ-secretase and the redistribution of presenilin 1 from lipid rafts. Moreover, 19,20-DHDP, but not the parent epoxide, was able to rescue the defective angiogenesis in sEH(-/-) mice as well as in animals lacking the Fbxw7 ubiquitin ligase, which demonstrate strong basal activity of the Notch signaling cascade. These studies demonstrate that retinal angiogenesis is regulated by a novel form of neuroretina-vascular interaction involving the sEH-dependent generation of a diol of DHA in Müller cells.
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