ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Macrophage epoxygenase determines a profibrotic transcriptome signature.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Supervised discovery of interpretable gene programs from single-cell data.Nature biotechnology · 2024Article
- Epoxyeicosatrienoic acid administration or soluble epoxide hydrolase inhibition attenuates renal fibrogenesis in obstructive nephropathy.American journal of physiology. Renal physiology · 2023Article
- Single cell transcriptomics in human osteoarthritis synovium and in silico deconvoluted bulk RNA sequencing.Osteoarthritis and cartilage · 2022Article
- Orally active epoxyeicosatrienoic acid analogs in hypertension and renal injury.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Cytochrome P450 2A6 is associated with macrophage polarization and is a potential biomarker for hepatocellular carcinoma.FEBS open bio · 2021Article
- Macrophage imaging and subset analysis using single-cell RNA sequencing.Nanotheranostics · 2021Article
- Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models.Frontiers in genetics · 2021Review
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Epoxy Fatty Acids: From Salt Regulation to Kidney and Cardiovascular Therapeutics: 2019 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Mechanism of Chronic Kidney Disease Progression and Novel Biomarkers: A Metabolomic Analysis of Experimental Glomerulonephritis.Metabolites · 2020Article
- Tracing tumorigenesis in a solid tumor model at single-cell resolution.Nature communications · 2020Article
- Digital expression explorer 2: a repository of uniformly processed RNA sequencing data.GigaScience · 2019Article
- New Lipid Mediators in Retinal Angiogenesis and Retinopathy.Frontiers in pharmacology · 2019Review
- Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis.Molecular metabolism · 2018Article
- Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function.Genetics · 2017Article
- Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet.Disease models & mechanisms · 2016Article
- CYP450-derived oxylipins mediate inflammatory resolution.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein.Disease models & mechanisms · 2016Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
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(-/-) macrophages have relatively increased peroxisome proliferator-activated receptor-γ 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(-/-) rats show upregulation of type I collagen following unilateral ureter obstruction of the kidney, and quantitative proteomics analysis (liquid chromatography-tandem 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.