ArticleAnnals of the rheumatic diseases2019
TNF-induced inflammatory genes escape repression in fibroblast-like synoviocytes: transcriptomic and epigenomic analysis.
Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 111 citations in OpenAlex.
- Targeting fibroblasts in immune mediated inflammatory diseases: a cellular basis for cure?Rheumatology (Oxford, England) · 2026Review
- LIN28A‒let-7b axis drives the aggressive and proinflammatory phenotype of rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2026Article
- Charge-reversal proteolysis polymers enable tissue-specific STING degradation in rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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- Epigenetic suppression of synovial inflammation and osteoclast differentiation in rheumatoid arthritis by I-BET762.Scientific reports · 2026Article
- Epigenetic alterations in rheumatoid arthritis: multilayer mechanisms and translational opportunities.Frontiers in immunology · 2026Review
- Multidimensional regulatory mechanisms and translational potential of epigenetic networks in the rheumatoid arthritis disease course.Frontiers in immunology · 2026Review
- A novel role of the TNF-α/p65/IRF1 axis in aggravating rheumatoid arthritis through the induction of fibroblast-like synoviocytes pyroptosis.Frontiers in pharmacology · 2026Article
- RNA-seq Based Transcriptome Analysis Reveals Role of Myoglobin in Rheumatoid Arthritis.Inflammation · 2025Article
- Selective CBP/EP300 Bromodomain Inhibitors: Novel Epigenetic Tools to Counter TNF-α-Driven Inflammation.JACS Au · 2025Article
- Fibroblasts in immune responses, inflammatory diseases and therapeutic implications.Nature reviews. Rheumatology · 2025Review
- Epigenomic landscapes define differential Janus kinases inhibitor sensitivity in IFN-γ-primed human macrophages.iScience · 2025Article
- GRK2 activates TRAF2-NF-Acta pharmaceutica Sinica. B · 2025Article
- Multiomics profiles of genome-wide alterations in H3K27ac in different lung lobes after acute graft-Frontiers in immunology · 2025Article
- Bromodomain and Extraterminal Protein Inhibition: A Novel Therapeutic Strategy in Arthritis.Journal of inflammation research · 2025Review
- Network-based pharmacology to predict the mechanism of qianghuo erhuang decoction in the treatment of rheumatoid arthritis.African health sciences · 2024Article
- Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis.Bioactive materials · 2024Article
- GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis.Acta pharmaceutica Sinica. B · 2024Article
- Is occupational noise associated with arthritis? Cross-sectional evidence from US population.BMC public health · 2024Article
- Sinulariolide Suppresses Inflammation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis and Mitigates Collagen-Induced Arthritis Symptoms in Mice.Journal of inflammation research · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe investigated genome-wide changes in gene expression and chromatin remodelling induced by tumour necrosis factor (TNF) in fibroblast-like synoviocytes (FLS) and macrophages to better understand the contribution of FLS to the pathogenesis of rheumatoid arthritis (RA).
methodsFLS were purified from patients with RA and CD14
resultsWe discovered 280 TNF-inducible arthritogenic genes which are transiently expressed and subsequently repressed in macrophages, but in RA, FLS are expressed with prolonged kinetics that parallel the unremitting kinetics of RA synovitis. 80 out of these 280 fibroblast-sustained genes (FSGs) that escape repression in FLS relative to macrophages were desensitised (tolerised) in macrophages. Epigenomic analysis revealed persistent H3K27 acetylation and increased chromatin accessibility in regulatory elements associated with FSGs in TNF-stimulated FLS. The accessible regulatory elements of FSGs were enriched in binding motifs for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interferon-regulatory factors (IRFs) and activating protein-1 (AP-1). Inhibition of bromodomain and extra-terminal motif (BET) proteins, which interact with histone acetylation, suppressed sustained induction of FSGs by TNF.
conclusionOur genome-wide analysis has identified the escape of genes from transcriptional repression in FLS as a novel mechanism potentially contributing to the chronic unremitting synovitis observed in RA. Our finding that TNF induces sustained chromatin activation in regulatory elements of the genes that escape repression in RA FLS suggests that altering or targeting chromatin states in FLS (eg, with inhibitors of BET proteins) is an attractive therapeutic strategy.
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