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10.4049/jimmunol.1402979 http://scihub22266oqcxt.onion/10.4049/jimmunol.1402979 C4417646!4417646 !25840911     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25840911 &cmd=llinks): Failed to open stream: HTTP request failed! 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Macrophage epoxygenase determines a profibrotic transcriptome signature |pdf=|usr=}}{{25840911 }} gab.com Text Macrophage epoxygenase determines a profibrotic transcriptome signature JO: J Immunol http://www.kidney.de/pget.php?&tw=1&pmid=25840911 #FOAvip 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-? 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. Twit Text FOAVip Macrophage epoxygenase determines a profibrotic transcriptome signature ????J Immunol http://www.kidney.de/pget.php?&tw=1&pmid=25840911 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25840911 #FOAvip English Wikipedia <ref>{{Cite pmid|25840911 }}</ref> Macrophage epoxygenase determines a profibrotic transcriptome signature #MMPMID25840911 Behmoaras J ; Diaz AG ; Venda L ; Ko JH ; Srivastava P ; Montoya A ; Faull P ; Webster Z ; Moyon B ; Pusey CD ; Abraham DJ ; Petretto E ; Cook TH ; Aitman TJ J Immunol 2015[May]; 194 (10 ): 4705-4716 PMID25840911 show ga 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-? 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. |Animals [MESH] |Blotting, Western [MESH] |Chromatography, Liquid [MESH] |Cytochrome P-450 CYP2J2 [MESH] |Cytochrome P-450 Enzyme System/*metabolism [MESH] |Cytochrome P450 Family 2 [MESH] |Disease Models, Animal [MESH] |Enzyme-Linked Immunosorbent Assay [MESH] |Fibrosis/*enzymology/*genetics [MESH] |Gene Knockout Techniques [MESH] |Glomerulonephritis/enzymology/genetics [MESH] |High-Throughput Nucleotide Sequencing [MESH] |Humans [MESH] |Macrophages/*enzymology [MESH] |Male [MESH] |RNA Interference [MESH] |Rats [MESH] |Rats, Inbred WKY [MESH] |Real-Time Polymerase Chain Reaction [MESH] |Tandem Mass Spectrometry [MESH]Macrophage epoxygenase determines a profibrotic transcriptome signatur(epmc).pdf DeepDyve Pubget Overpricing