Imperial College London
Alternate

DrPrashantSrivastava

Faculty of Medicine, National Heart & Lung Institute

Lecturer in Cardiovascular Bioinformatics and Medical Statis
 
 
 
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Contact

 

prashant.srivastava

 
 
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Location

 

337ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Behmoaras:2015:10.4049/jimmunol.1402979,
author = {Behmoaras, J and Diaz, AG and Venda, L and Ko, J-H and Srivastava, P and Montoya, A and Faull, P and Webster, Z and Moyon, B and Pusey, CD and Abraham, DJ and Petretto, E and Cook, TH and Aitman, TJ},
doi = {10.4049/jimmunol.1402979},
journal = {Journal of Immunology},
pages = {4705--4716},
title = {Macrophage Epoxygenase Determines a Profibrotic Transcriptome Signature},
url = {http://dx.doi.org/10.4049/jimmunol.1402979},
volume = {194},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Behmoaras,J
AU  - Diaz,AG
AU  - Venda,L
AU  - Ko,J-H
AU  - Srivastava,P
AU  - Montoya,A
AU  - Faull,P
AU  - Webster,Z
AU  - Moyon,B
AU  - Pusey,CD
AU  - Abraham,DJ
AU  - Petretto,E
AU  - Cook,TH
AU  - Aitman,TJ
DO  - 10.4049/jimmunol.1402979
EP  - 4716
PY  - 2015///
SN  - 1550-6606
SP  - 4705
TI  - Macrophage Epoxygenase Determines a Profibrotic Transcriptome Signature
T2  - Journal of Immunology
UR  - http://dx.doi.org/10.4049/jimmunol.1402979
VL  - 194
ER  -
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