 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Dec 16, 2021 |
| Title |
Arginine methyltransferase regulates monocyte extravasation and function |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Extravasation of monocytes into tissue and to the site of injury is a fundamental immunological process underlying a variety of innate inflammatory responses across multiple organ systems, which requires rapid responses via post translational modifications (PTM) of proteins. Specifically, methylation of protein by arginine methyltransferases (PRMTs) is an epigenetic PTM implicated in inflammatory responses. However, how methyltransferases drive immune regulation particularly in the lung, the resultant tissue injury and whether this might be of therapeutic value has remained unclear. Here, we demonstrate that PRMT7 was increased in the lung of chronic obstructive pulmonary disease (COPD) patients and positively correlated with tissue injury. Accordingly, in clinically relevant models of COPD, lung fibrosis and skin injury, mice with reduced expression of PRMT7 were protected against disease development, due to decreased recruitment of pro-inflammatory monocytes to the site of injury. Mechanistically, we discovered in monocytes activation of NF-κB/RelA induces PRMT7, promoting mono-methylation of histones, which crucially regulates RAP1A and subsequent adhesion and migration ability. Furthermore, in pro-inflammatory monocytes, ALOX5 derived LTB4 induced ACSL4 expression in lung epithelial cells and consequently sensitized towards ferroptosis, thus aggravating tissue injury. Conclusively, specific targeting of arginine mono-methylation offers yet-unappreciated therapeutic potential against monocyte-driven inflammatory conditions.
|
| |
|
| Overall design |
Single-cell transcriptomics experiment after prolonged cigarette smoke exposure
|
| |
|
| Contributor(s) |
Conlon TM, Günsel GG, Jeridi A, Lang NJ, Ansari M, Strunz M, Angelidis I, Schiller HB, Yildirim A |
| Citation(s) |
35031603 |
| |
| Submission date |
Sep 29, 2021 |
| Last update date |
Feb 02, 2022 |
| Contact name |
Meshal Ansari |
| Organization name |
Helmholtz Zentrum Munich
|
| Street address |
Ingolstädter Landstrasse 1
|
| City |
Neuherberg |
| State/province |
Bavaria |
| ZIP/Postal code |
85764 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (16)
|
|
| Relations |
| BioProject |
PRJNA767361 |
| SRA |
SRP339294 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE185006_MonocyteExtravasation.h5ad.gz |
6.9 Gb |
(ftp)(http) |
H5AD |
| GSE185006_MonocyteExtravasation_MNPs.h5ad.gz |
613.6 Mb |
(ftp)(http) |
H5AD |
| GSE185006_MonocyteExtravasation_MonoMacro.h5ad.gz |
288.8 Mb |
(ftp)(http) |
H5AD |
| GSE185006_MonocyteExtravasation_barcodes.txt.gz |
328.3 Kb |
(ftp)(http) |
TXT |
| GSE185006_MonocyteExtravasation_cells_metadata.txt.gz |
1.8 Mb |
(ftp)(http) |
TXT |
| GSE185006_MonocyteExtravasation_genes.txt.gz |
76.8 Kb |
(ftp)(http) |
TXT |
| GSE185006_MonocyteExtravasation_raw_counts.mtx.gz |
186.5 Mb |
(ftp)(http) |
MTX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...