RGD Reference Report - Macrophage epoxygenase determines a profibrotic transcriptome signature. - Rat Genome Database

Send us a Message



 Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap)  (beta) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer) Overgo Probe Designer
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease COVID-19 Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes GERRC (Gene Editing Rat Resource Center) Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Poster Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Macrophage epoxygenase determines a profibrotic transcriptome signature.

Authors: Behmoaras, Jacques  Diaz, Ana Garcia  Venda, Lara  Ko, Jeong-Hun  Srivastava, Prashant  Montoya, Alex  Faull, Peter  Webster, Zoe  Moyon, Ben  Pusey, Charles D  Abraham, David J  Petretto, Enrico  Cook, Terence H  Aitman, Timothy J 
Citation: Behmoaras J, etal., J Immunol. 2015 May 15;194(10):4705-16. doi: 10.4049/jimmunol.1402979. Epub 2015 Apr 3.
RGD ID: 12904676
Pubmed: PMID:25840911   (View Abstract at PubMed)
PMCID: PMC4417646   (View Article at PubMed Central)
DOI: DOI:10.4049/jimmunol.1402979   (Journal Full-text)

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.



Disease Annotations    
nephritis  (IMP,ISO)
ureteral obstruction  (IMP,ISO)

Gene Ontology Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Cyp2j4  (cytochrome P450, family 2, subfamily j, polypeptide 4)
Cyp2j4em1Sage  (cytochrome P450, family 2, subfamily j, polypeptide 4, ZFN induced mutant 1, Sage)

Genes (Mus musculus)
Cyp2j9  (cytochrome P450, family 2, subfamily j, polypeptide 9)

Genes (Homo sapiens)
CYP2J2  (cytochrome P450 family 2 subfamily J member 2)

Strains
WKY-Cyp2j4em1Sage/Tja  (NA)

Objects referenced in this article
Gene Gh1 growth hormone 1 Rattus norvegicus

Additional Information