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Volume 11
Issue 12
10.3390/biomedicines11123188
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Article

BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts

by
Tanja Seifritz
1,
Matthias Brunner
2,3,
Eva Camarillo Retamosa
1,
Malgorzata Maciukiewicz
1,2,3,
Monika Krošel
1,4,5,
Larissa Moser
1,
Thomas Züllig
1,
Matija Tomšič
4,5,
Oliver Distler
1,
Caroline Ospelt
1 and
Kerstin Klein
2,3,*
1
Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland
2
Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland
3
Department for BioMedical Research, University of Bern, 3008 Bern, Switzerland
4
Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
5
Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Biomedicines 2023, 11(12), 3188; https://doi.org/10.3390/biomedicines11123188
Submission received: 7 November 2023 / Revised: 18 November 2023 / Accepted: 24 November 2023 / Published: 30 November 2023
(This article belongs to the Special Issue Fibroblasts: Insights from Molecular and Pathophysiology Perspectives)
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Abstract

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.
Keywords: synovial fibroblast; arthritis; bromo domain; inflammation; stress response synovial fibroblast; arthritis; bromo domain; inflammation; stress response

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MDPI and ACS Style

Seifritz, T.; Brunner, M.; Camarillo Retamosa, E.; Maciukiewicz, M.; Krošel, M.; Moser, L.; Züllig, T.; Tomšič, M.; Distler, O.; Ospelt, C.; et al. BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts. Biomedicines 2023, 11, 3188. https://doi.org/10.3390/biomedicines11123188

AMA Style

Seifritz T, Brunner M, Camarillo Retamosa E, Maciukiewicz M, Krošel M, Moser L, Züllig T, Tomšič M, Distler O, Ospelt C, et al. BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts. Biomedicines. 2023; 11(12):3188. https://doi.org/10.3390/biomedicines11123188

Chicago/Turabian Style

Seifritz, Tanja, Matthias Brunner, Eva Camarillo Retamosa, Malgorzata Maciukiewicz, Monika Krošel, Larissa Moser, Thomas Züllig, Matija Tomšič, Oliver Distler, Caroline Ospelt, and et al. 2023. "BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts" Biomedicines 11, no. 12: 3188. https://doi.org/10.3390/biomedicines11123188

APA Style

Seifritz, T., Brunner, M., Camarillo Retamosa, E., Maciukiewicz, M., Krošel, M., Moser, L., Züllig, T., Tomšič, M., Distler, O., Ospelt, C., & Klein, K. (2023). BRD3 Regulates the Inflammatory and Stress Response in Rheumatoid Arthritis Synovial Fibroblasts. Biomedicines, 11(12), 3188. https://doi.org/10.3390/biomedicines11123188

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