{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:30:29Z","timestamp":1789050629087,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Abnormal activation and proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) play an important role in rheumatoid arthritis (RA), the mechanism of which remains elusive. The purpose of our study is to comprehensively explore the mechanism of the Nrf2\u2010GPX4 pathway\u2010mediated abnormal RASF activation in RA. Here, we found that Nrf2 and GPX4 protein expression levels were downregulated in the synovial tissues of complete Freund's adjuvant (CFA)\u2010induced adjuvant\u2010induced arthritis (AIA) rats compared with those in control rats. However, Nrf2\u2010GPX4 activation by the Nrf2 activator CDDO\u2010EA could abrogate the CFA\u2010induced macrophage ferroptosis and inflammatory response, as suggested by decreased levels of 5\u2010HT, TNF\u2010\u03b1, IL\u20106, MDA, Fe\n                    <jats:sup>2+<\/jats:sup>\n                    , and lipid peroxidation, yet increased levels of SOD and GSH. As such, Nrf2\u2010GPX4 relieved CFA\u2010induced arthritis in rats. We further found that Nrf2\u2010GPX4 activation arrested macrophage ferroptosis and M1 polarization, and restrained RASF proliferation in vitro. More strikingly, these effects of Nrf2\u2010GPX4 could be partially abolished by the ferroptosis inducer RSL\u20103. In conclusion, our study provides the first evidence that activated Nrf2\u2010GPX4 can retard RA by suppressing macrophage ferroptosis, M1 polarization, and RASF proliferation. These results provide a new perspective for understanding RA pathogenesis and finding new therapeutic targets.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70539","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T14:58:17Z","timestamp":1761663497000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Nrf2\u2010GPX4 Pathway Provides Protection Against Rheumatoid Arthritis via Inhibition of Macrophage Ferroptosis\u2010Mediated Inflammation and Synovial Fibroblast Proliferation"],"prefix":"10.1002","volume":"39","author":[{"given":"Bingxue","family":"Liang","sequence":"first","affiliation":[{"name":"College of Acupuncture and Tuina Chongqing University of Chinese Medicine Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Li","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina Chongqing University of 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