{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:26:28Z","timestamp":1788459988698,"version":"build-2803163510"},"reference-count":30,"publisher":"S. Karger AG","issue":"8","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"abstract":"<jats:p>Introduction: Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder and a predominant cause of potentially treatable functional disability. Adenosine deaminase acting on RNA 1 (ADAR1), as an RNA-editing enzyme, can regulate circular RNAs and fibroblast-like synoviocyte (FLS)-derived exosomal circFTO has been proposed as a contributor to RA. This study was dedicated to elaborate the role of ADAR1 in RA and the association between ADAR1 and circFTO. Methods: Reverse transcription-quantitative PCR (RT-qPCR) examined circFTO, fat mass, and obesity-associated protein (FTO), DExH-box helicase 9 (DHX9), ADAR1, and Quaking (QKI) expressions in RA-FLSs and human fibroblast-like synoviocytes (HFLSs), and circFTO expression in RA-FLS- or HFLS-derived exosomes. In severe combined immunodeficiency (SCID) mice engrafted with human cartilage and rheumatoid synovium tissue (SCID-HuRAg), the in vivo imaging technique was adopted to track the distribution and migration of RA-FLSs and HFLSs. Hematoxylin and eosin staining and Safranin-O staining measured the severity of RA and engrafted cartilage degradation. Immunohistochemistry assessed the expression of inflammation-, anabolic-, and catabolic-related genes. Also, RT-qPCR examined the expressions of circFTO, miR-548a-3p, heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), anabolic- and catabolic-related genes. Results: ADAR1 was lowly expressed in RA-FLSs and ADAR1 silencing reduced circFTO expression in RA-FLS-derived exosomes. In vivo, RA-FLSs were widely distributed, and the migration capability was enhanced compared with HFLSs. ADAR1 overexpression efficiently decreased arthritis severity and attenuated cartilage degradation and inflammatory response in SCID-HuRAg mice injected with RA-FLSs. Besides, ADAR1 could decrease circFTO and hnRNPA2B1 expressions while elevating miR-548a-3p expression, particularly in SCID-HuRAg mice injected with RA-FLSs. Conclusion: To summarize, our findings identify ADAR1 as a potential treatment target for RA at least partially via regulating circFTO.<\/jats:p>","DOI":"10.1159\/000547802","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:00:38Z","timestamp":1759939238000},"page":"868-880","source":"Crossref","is-referenced-by-count":2,"title":["RNA-Editing Enzyme ADAR1 Attenuates Rheumatoid Arthritis via Regulating Fibroblast-Like Synoviocyte-Derived Exosomal circFTO"],"prefix":"10.1159","volume":"187","author":[{"given":"Yuxuan","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30173-8"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.7326\/AITC201901010"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102776"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102735"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27860"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-12-43"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.12.009"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.01.005"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.1665"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.3390\/genes10010012"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2024.102195"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1261\/rna.079953.124"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0243-y"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00779-x"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110549"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2023.156418"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-024-03290-0"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-0413-5"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1002\/art.40504"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3682-4_2"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2050"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1177\/11779322221088725"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.559138"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-024-01051-8"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2024.06.006"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.3390\/genes8010041"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.08.002"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.12.035"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26659"}],"container-title":["International Archives of Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000547802","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T16:01:44Z","timestamp":1784217704000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000547802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,8]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,7,16]]},"published-print":{"date-parts":[[2026,8,5]]}},"URL":"https:\/\/doi.org\/10.1159\/000547802","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.30305644","asserted-by":"subject"}]},"ISSN":["1018-2438","1423-0097"],"issn-type":[{"value":"1018-2438","type":"print"},{"value":"1423-0097","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,8]]}}}