{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:50:55Z","timestamp":1790394655338,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Epoxygenases belong to the cytochrome P450 family. They generate epoxyeicosatrienoic acids, which are known to have anti-inflammatory effects, but little is known about their role in macrophage function. By high-throughput sequencing of RNA in primary macrophages derived from rodents and humans, we establish the relative expression of epoxygenases in these cells. Zinc-finger nuclease-mediated targeted gene deletion of the major rat macrophage epoxygenase Cyp2j4 (ortholog of human CYP2J2) resulted in reduced epoxyeicosatrienoic acid synthesis. Cyp2j4\u2212\/\u2212 macrophages have relatively increased peroxisome proliferator-activated receptor-\u03b3 levels and show a profibrotic transcriptome, displaying overexpression of a specific subset of genes (260 transcripts) primarily involved in extracellular matrix, with fibronectin being the most abundantly expressed transcript. Fibronectin expression is under the control of epoxygenase activity in human and rat primary macrophages. In keeping with the in vitro findings, Cyp2j4\u2212\/\u2212 rats show upregulation of type I collagen following unilateral ureter obstruction of the kidney, and quantitative proteomics analysis (liquid chromatography\u2013tandem mass spectrometry) showed increased renal type I collagen and fibronectin protein abundance resulting from experimentally induced crescentic glomerulonephritis in these rats. Taken together, these results identify the rat epoxygenase Cyp2j4 as a determinant of a profibrotic macrophage transcriptome that could have implications in various inflammatory conditions, depending on macrophage function.<\/jats:p>","DOI":"10.4049\/jimmunol.1402979","type":"journal-article","created":{"date-parts":[[2015,4,4]],"date-time":"2015-04-04T01:06:05Z","timestamp":1428109565000},"page":"4705-4716","source":"Crossref","is-referenced-by-count":29,"title":["Macrophage Epoxygenase Determines a Profibrotic Transcriptome Signature"],"prefix":"10.1093","volume":"194","author":[{"given":"Jacques","family":"Behmoaras","sequence":"first","affiliation":[{"name":"Centre for Complement and Inflammation Research, Imperial College London , London W12 0NN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Garcia","family":"Diaz","sequence":"additional","affiliation":[{"name":"Physiological Genomics and Medicine Group, MRC Clinical Sciences 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