ArticleArthritis research & therapy2020
Intervening upregulated SLC7A5 could mitigate inflammatory mediator by mTOR-P70S6K signal in rheumatoid arthritis synoviocytes.
Article in Arthritis research & therapy, 2020. 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, 32 citations in OpenAlex.
- Pharmacological Inhibition of the PI3K/AKT/mTOR Pathway in Rheumatoid Arthritis Synoviocytes: A Systematic Review and Meta-Analysis (Preclinical).Pharmaceuticals (Basel, Switzerland) · 2025Review
- Research advances in branched-chain amino acid metabolism in tumors.Molecular and cellular biochemistry · 2025Review
- TRIM35 triggers cardiac remodeling by regulating SLC7A5-mediated amino acid transport and mTORC1 activation in fibroblasts.Cell communication and signaling : CCS · 2024Article
- Identification of potential biomarkers from amino acid transporter in the activation of hepatic stellate cells via bioinformatics.Frontiers in genetics · 2024Article
- Identification of key biomarkers related to fibrocartilage chondrocytes for osteoarthritis based on bulk, single-cell transcriptomic data.Frontiers in immunology · 2024Article
- Identification of genetic variants associated with anterior cruciate ligament rupture and AKC standard coat color in the Labrador Retriever.BMC genomic data · 2023Article
- Tryptophan metabolism and disposition in cancer biology and immunotherapy.Bioscience reports · 2022Article
- Epigenetic Regulation of Nutrient Transporters in Rheumatoid Arthritis Fibroblast-like Synoviocytes.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- Cellular metabolic adaptations in rheumatoid arthritis and their therapeutic implications.Nature reviews. Rheumatology · 2022Review
- Metabolites as drivers and targets in rheumatoid arthritis.Clinical and experimental immunology · 2022Article
- Genetic Deficiency of Indoleamine 2,3-dioxygenase Aggravates Vascular but Not Liver Disease in a Nonalcoholic Steatohepatitis and Atherosclerosis Comorbidity Model.International journal of molecular sciences · 2022Article
- Inside the Joint of Inflammatory Arthritis Patients: Handling and Processing of Synovial Tissue Biopsies for High Throughput Analysis.Frontiers in medicine · 2022Review
- Cross-Tissue Analysis Using Machine Learning to Identify Novel Biomarkers for Knee Osteoarthritis.Computational and mathematical methods in medicine · 2022Article
- Solute carrier nutrient transporters in rheumatoid arthritis fibroblast-like synoviocytes.Frontiers in immunology · 2022Review
- Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following high-intensity interval training in persons with rheumatoid arthritis.Arthritis research & therapy · 2021Article
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe disruption of metabolic events and changes to nutrient and oxygen availability due to sustained inflammation in RA increases the demand of bioenergetic and biosynthetic processes within the damaged tissue. The current study aimed to understand the molecular mechanisms of SLC7A5 (amino acid transporter) in synoviocytes of RA patients.
methodsSynovial tissues were obtained from OA and RA patients. Fibroblast-like synoviocytes (FLS) were isolated, and SLC7A5 expression was examined by using RT-qPCR, immunofluorescence, and Western blotting. RNAi and antibody blocking treatments were used to knockdown SLC7A5 expression or to block its transporter activities. mTOR activity assay and MMP expression levels were monitored in RA FLS under amino acid deprivation or nutrient-rich conditions.
resultsRA FLS displayed significantly upregulated expression of SLC7A5 compared to OA FLS. Cytokine IL-1β was found to play a crucial role in upregulating SLC7A5 expression via the NF-κB pathway. Intervening SLC7A5 expression with RNAi or blocking its function by monoclonal antibody ameliorated MMP3 and MMP13 protein expression. Conversely, upregulation of SLC7A5 or tryptophan supplementation enhanced mTOR-P70S6K signals which promoted the protein translation of MMP3 and MMP13 in RA FLS.
conclusionActivated NF-κB pathway upregulates SLC7A5, which enhances the mTOR-P70S6K activity and MMP3 and MMP13 expression in RA FLS.
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