ArticleArthritis research & therapy2017
Glutaminase 1 plays a key role in the cell growth of fibroblast-like synoviocytes in rheumatoid arthritis.
Article in Arthritis research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 136 citations in OpenAlex.
- Metabolic Complications in Autoimmune and Autoinflammatory Diseases: Pathophysiology, Clinical Implications, and Therapeutic Perspectives.Journal of clinical medicine · 2026Review
- Glutamine-dependent biosynthetic pathways fuel autoreactive T and B cells in Foxp3 deficiency-mediated disease.JCI insight · 2026Article
- Role of the PI3K/AKT signaling pathway in regulating gene expression in rheumatoid arthritis (Review).Molecular medicine reports · 2026Review
- Convallatoxin ameliorates fibroblast-like synoviocytes-mediated synovial inflammation and joint destruction in rheumatoid arthritis by targeting IDH1.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Immunometabolic reprogramming in rheumatoid arthritis: the epitranscriptomic role of N6-methyladenosine in innate and adaptive immunity.Frontiers in immunology · 2026Review
- Immunometabolism in rheumatoid arthritis: mechanisms, biomarkers, and the path to precision medicine.Frontiers in immunology · 2026Review
- Roles of immune cell metabolism in rheumatoid arthritis.Frontiers in immunology · 2026Review
- Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint.Journal of translational autoimmunity · 2025Article
- The role of epigenetic regulation in cuproptosis, ferroptosis and NETosis in the pathogenesis of autoimmune diseases.Apoptosis : an international journal on programmed cell death · 2025Review
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Effects of glutaminase 1 inhibitor on rotator cuff derived cells: a preliminary report in 12 patients.BMC musculoskeletal disorders · 2025Article
- Mitochondria as a Disease-Relevant Organelle in Rheumatoid Arthritis: A Key Breakout in Fight Against the Disease.Biomedicines · 2025Review
- Review
- Unraveling the causal nexus of cathepsins and rheumatoid arthritis: Insights from a two-sample Mendelian randomization framework.Medicine · 2025Article
- Unveiling the Therapeutic Potential: Targeting Fibroblast-like Synoviocytes in Rheumatoid Arthritis.Expert reviews in molecular medicine · 2025Review
- Fibroblasts in immune responses, inflammatory diseases and therapeutic implications.Nature reviews. Rheumatology · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- The Potential Utility of (2S,4R)-4-[Molecular imaging and biology · 2025Article
- Metabolic reprogramming: the central mechanism driving inflammatory polarization in rheumatoid arthritis and the regulatory role of traditional Chinese medicine.Frontiers in immunology · 2025Review
- Specific inhibition of glutamine synthase involved in the metabolic pathway of amino acids is associated with anti-arthritic effects of sinomenine hydrochloride.Frontiers in cell and developmental biology · 2025Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundThe recent findings of cancer-specific metabolic changes, including increased glucose and glutamine consumption, have provided new therapeutic targets for consideration. Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients exhibit several tumor cell-like characteristics; however, the role of glucose and glutamine metabolism in the aberrant proliferation of these cells is unclear. Here, we evaluated the role of these metabolic pathways in RA-FLS proliferation and in autoimmune arthritis in SKG mice.
methodsThe expression of glycolysis- or glutaminolysis-related enzymes was evaluated by real-time polymerase chain reaction (PCR) and Western blotting, and the intracellular metabolites were evaluated by metabolomic analyses. The effects of glucose or glutamine on RA-FLS cell growth were investigated using glucose- or glutamine-free medium. Glutaminase (GLS)1 small interfering RNA (siRNA) and the GLS1 inhibitor compound 968 were used to inhibit GLS1 in RA-FLS, and compound 968 was used to study the effect of GLS1 inhibition in zymosan A-injected SKG mice.
resultsGLS1 expression was increased in RA-FLS, and metabolomic analyses revealed that glutamine metabolism was increased in RA-FLS. RA-FLS proliferation was reduced under glutamine-deprived, but not glucose-deprived, conditions. Cell growth of RA-FLS was inhibited by GLS1 siRNA transfection or GLS1 inhibitor treatment. Treating RA-FLS with either interleukin-17 or platelet-derived growth factor resulted in increased GLS1 levels. Compound 968 ameliorated the autoimmune arthritis and decreased the number of Ki-67-positive synovial cells in SKG mice.
conclusionsOur results suggested that glutamine metabolism is involved in the pathogenesis of RA and that GLS1 plays an important role in regulating RA-FLS proliferation, and may be a novel therapeutic target for RA.
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