{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:30:28Z","timestamp":1786977028392,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004410","name":"European Molecular Biology Organization","doi-asserted-by":"publisher","award":["ALTF\u2010960\u20102018"],"award-info":[{"award-number":["ALTF\u2010960\u20102018"]}],"id":[{"id":"10.13039\/100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01AR077111"],"award-info":[{"award-number":["K01AR077111"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS047101"],"award-info":[{"award-number":["NS047101"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS087611"],"award-info":[{"award-number":["NS087611"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AR073761"],"award-info":[{"award-number":["P30AR073761"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AR073324"],"award-info":[{"award-number":["R01AR073324"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AR064194"],"award-info":[{"award-number":["T32AR064194"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Since previous studies indicate that metabolism is altered in rheumatoid arthritis (RA) fibroblast\u2010like synoviocytes (FLS), we undertook this study to determine if changes in the genome\u2010wide chromatin and DNA states in genes associated with nutrient transporters could help to identify activated metabolic pathways in RA FLS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from a previous comprehensive epigenomic study in FLS were analyzed to identify differences in genome\u2010wide 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\u2010839, a glutaminase inhibitor. We performed\n                      <jats:sup>1<\/jats:sup>\n                      H nuclear magnetic resonance to quantify metabolites.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The unbiased pathway analysis demonstrated that solute carrier\u2013mediated transmembrane transport was one pathway associated with differences in at least 4 genome\u2010wide states or gene transcription. Thirty\u2010four 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\u2010839 demonstrated decreased RA FLS invasion and proliferation. Finally, we found enrichment of motifs for c\u2010Myc in several nutrient transporters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that changes in the epigenetic landscape of genes are related to nutrient transporters, and metabolic pathways can be used to identify RA\u2010specific targets, including critical solute carrier transporters, enzymes, and transcription factors, to develop novel therapeutic agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42077","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T02:08:52Z","timestamp":1644199732000},"page":"1159-1171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Epigenetic Regulation of Nutrient Transporters in Rheumatoid Arthritis Fibroblast\u2010like Synoviocytes"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3028-0846","authenticated-orcid":false,"given":"Alyssa","family":"Torres","sequence":"first","affiliation":[{"name":"University of California  San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Pedersen","sequence":"additional","affiliation":[{"name":"University of California  San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidoro","family":"Cobo","sequence":"additional","affiliation":[{"name":"University of California  San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizi","family":"Ai","sequence":"additional","affiliation":[{"name":"University of California  San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Coras","sequence":"additional","affiliation":[{"name":"University of California, San Diego, and Autonomous University of Barcelona  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Murillo\u2010Saich","sequence":"additional","affiliation":[{"name":"University of California  San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyrid","family":"Nygaard","sequence":"additional","affiliation":[{"name":"University of California  San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Sanchez\u2010Lopez","sequence":"additional","affiliation":[{"name":"VA Medical Center  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Murphy","sequence":"additional","affiliation":[{"name":"VA Medical Center  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"University of California  San Diego"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary 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