ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Epigenetic Regulation of Nutrient Transporters in Rheumatoid Arthritis Fibroblast-like Synoviocytes.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- Stereoselective design of amino acid bioconjugates: targeting strategies and physicochemical optimization.RSC medicinal chemistry · 2026Review
- Immunometabolic reprogramming in rheumatoid arthritis: the epitranscriptomic role of N6-methyladenosine in innate and adaptive immunity.Frontiers in immunology · 2026Review
- RNA Binding Protein YTHDF2 Inhibits Synovial Fibroblast Inflammation and Bone Injury in Rheumatoid Arthritis by Reducing the mRNA Stability of IL-6R.The Kaohsiung journal of medical sciences · 2025Article
- Association of glutamine metabolites in synovial fluid with the severity of temporomandibular joint osteoarthritis.BMC musculoskeletal disorders · 2025Article
- Integrated analysis of the relationship between metabolic pathways and immune infiltration in rheumatoid arthritis.Frontiers in immunology · 2025Article
- Article
- Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders.Signal transduction and targeted therapy · 2024Review
- Dual inhibition of glycolysis and glutaminolysis for synergistic therapy of rheumatoid arthritis.Arthritis research & therapy · 2023Article
- Bovine tumor necrosis factor-alpha Increases IL-6, IL-8, and PGE2 in bovine fibroblast-like synoviocytes by metabolic reprogramming.Scientific reports · 2023Article
- Synovial tissue metabolomic profiling reveal biomarkers of synovial inflammation in patients with osteoarthritis.Osteoarthritis and cartilage open · 2022Article
- Docking and Molecular Dynamics Study to Identify Novel Phytobiologics fromLife (Basel, Switzerland) · 2022Article
- Mitochondrial Dysfunction and Oxidative Stress in Rheumatoid Arthritis.Antioxidants (Basel, Switzerland) · 2022Review
- Phenotype-Genotype analysis of caucasian patients with high risk of osteoarthritis.Frontiers in genetics · 2022Article
- Solute carrier nutrient transporters in rheumatoid arthritis fibroblast-like synoviocytes.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveSince previous studies indicate that metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), we undertook this study to determine if changes in the genome-wide chromatin and DNA states in genes associated with nutrient transporters could help to identify activated metabolic pathways in RA FLS.
methodsData from a previous comprehensive epigenomic study in FLS were analyzed to identify differences in genome-wide states and gene transcription between RA and osteoarthritis. We utilized the single nearest genes to regions of interest for pathway analyses. Homer promoter analysis was used to identify enriched motifs for transcription factors. The role of solute carrier transporters and glutamine metabolism dependence in RA FLS was determined by small interfacing RNA knockdown, functional assays, and incubation with CB-839, a glutaminase inhibitor. We performed
resultsThe unbiased pathway analysis demonstrated that solute carrier-mediated transmembrane transport was one pathway associated with differences in at least 4 genome-wide states or gene transcription. Thirty-four transporters of amino acids and other nutrients were associated with a change in at least 4 epigenetic marks. Functional assays revealed that solute carrier family 4 member 4 (SLC4A4) was critical for invasion, and glutamine was sufficient as an alternate source of energy to glucose. Experiments with CB-839 demonstrated decreased RA FLS invasion and proliferation. Finally, we found enrichment of motifs for c-Myc in several nutrient transporters.
conclusionOur findings demonstrate that changes in the epigenetic landscape of genes are related to nutrient transporters, and metabolic pathways can be used to identify RA-specific targets, including critical solute carrier transporters, enzymes, and transcription factors, to develop novel therapeutic agents.
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