|
| Status |
Public on Feb 10, 2015 |
| Title |
Macrophage epoxygenase determines a pro-fibrotic transcriptomesignature |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Epoxygenases belong to the cytochrome P450 family and they generate epoxyeicosatrienoic acids (EETs) known to have anti-inflammatory effects but little is known about their role in macrophage function. By high-throughput sequencing of RNA (RNA-seq) in primary macrophages derived fromrodents and humans, we establish the relative expression of epoxygenases in these cells. Zinc-finger nuclease-mediated targeted gene deletion of the major ratmacrophage epoxygenaseCyp2j4 (orthologue of human CYP2J2),resulted inreduced EET synthesis. Cyp2j4-/-macrophages have relatively increased PPARĪ³ levels and show a pro-fibrotic transcriptome,displayingover-expression 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 invitro findings, Cyp2j4-/- rats show up-regulation of type I collagen following unilateral ureter obstruction (UUO) of the kidney and quantitative proteomics analysis (LC-MS/MS) 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 pro-fibrotic macrophage transcriptome that could have implications in various inflammatory conditions depending on macrophage function.
|
| |
|
| Overall design |
Gene expression profile generated for macrophages in wild type and Cyp2j4 KO WKY rats
|
| |
|
| Contributor(s) |
Behmoaras J, Srivastava P |
| Citation(s) |
25840911 |
| Submission date |
Feb 06, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Jacques Behmoaras |
| E-mail(s) |
jacques.behmoaras@imperial.ac.uk
|
| Organization name |
Imperial College
|
| Department |
Centre for Complement and Inflammation Research (CCIR),
|
| Street address |
Du Cane road
|
| City |
London |
| ZIP/Postal code |
W12 0NN |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA274942 |
| SRA |
SRP053358 |
Less...
More...