Seifritz, Tanja; Brunner, Matthias; Camarillo Retamosa, Eva; Maciukiewicz, Malgorzata; Krošel, Monika; Moser, Larissa; Züllig, Thomas; Tomšič, Matija; Distler, Oliver; Ospelt, Caroline; Klein, Kerstin (2023). BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts. Biomedicines, 11(12) MDPI 10.3390/biomedicines11123188
|
Text
biomedicines-11-03188.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (4MB) | Preview |
BACKGROUND
Individual functions of members of the bromodomain (BRD) and extra-terminal (BET) protein family underlying the anti-inflammatory effects of BET inhibitors in rheumatoid arthritis (RA) are incompletely understood. Here, we aimed to analyze the regulatory functions of BRD3, an understudied member of the BET protein family, in RA synovial fibroblasts (FLS).
METHODS
BRD3 was silenced in FLS prior to stimulation with TNF. Alternatively, FLS were treated with I-BET. Transcriptomes were analyzed by RNA sequencing (RNAseq), followed by pathway enrichment analysis. We confirmed results for selective target genes by real-time PCR, ELISA, and Western blotting.
RESULTS
BRD3 regulates the expression of several cytokines and chemokines in FLS, and positively correlates with inflammatory scores in the RA synovium. In addition, RNAseq pointed to a profound role of BRD3 in regulating FLS proliferation, metabolic adaption, and response to stress, including oxidative stress, and autophagy.
CONCLUSIONS
BRD3 acts as an upstream regulatory factor that integrates the response to inflammatory stimuli and stress conditions in FLS and executes many functions of BET proteins that have previously been identified using pan-BET inhibitors.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology |
UniBE Contributor: |
Brunner, Matthias, Klein, Kerstin |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2227-9059 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
27 Dec 2023 15:34 |
Last Modified: |
29 Dec 2023 05:54 |
Publisher DOI: |
10.3390/biomedicines11123188 |
PubMed ID: |
38137409 |
Uncontrolled Keywords: |
arthritis bromo domain inflammation stress response synovial fibroblast |
BORIS DOI: |
10.48350/190751 |
URI: |
https://boris.unibe.ch/id/eprint/190751 |
Actions (login required)
 |
Edit item |