{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:31:50Z","timestamp":1789608710175,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":353,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070593"],"award-info":[{"award-number":["82070593"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770585"],"award-info":[{"award-number":["81770585"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LD21H030002"],"award-info":[{"award-number":["LD21H030002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n                    Autoimmune hepatitis (AIH) is an inflammatory autoimmune disease of the liver. Oxidative stress triggered by reactive oxygen radicals is a common pathophysiological basis for the pathogenesis of many liver diseases, and ferroptosis is associated with the toxic accumulation of reactive oxygen species. The signaling transduction pathways responsible for iron processing and lipid\u2010peroxidation mechanisms are believed to drive ferroptosis. However, the specific mechanisms regulating ferroptosis remain unclear. The aims of this investigation were to identify the possible effector functions of ferroptosis, based on glutathione peroxidase 4 (GPX4) regulation in an S100\u2010induced autoimmune hepatitis mouse model and hepatocyte injury models. The S100 liver antigen\u2010induced AIH mouse model was used to detect ferroptotic biomarkers using western blotting. Upregulated levels of cyclooxygenase2 (COX2) and Acyl\u2010Coenzyme A synthase long\u2010chain family member 4 (ACSL4) were observed in the S100\u2010induced AIH model group, while levels of GPX4 and ferritin heavy chain 1 (FTH1) were downregulated (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). The expression profiles of COX2, ACSL4, GPX4, and FTH1 were restored following the administration of ferrostatin\u20101. In addition, Nrf2 and HO\u20101 levels in the S100\u2010induced AIH model mice after treatment with ferrostatin\u20101 were downregulated compared to the nonferrostatin\u20101\u2010treated S100\u2010induced AIH model mice (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.05). Moreover, COX2 and ACSL4 levels were significantly upregulated, with significant FTH1 downregulation, in the AIH model mice when liver\u2010specific GPX4 was silenced using AAV8 constructs. These data indicate that inhibition of ferroptosis significantly ameliorated the influence of AIH on the Nuclear factor E2\u2010related factor 2 (Nrf2)\/Heme oxygenase\u20101 (HO\u20101) signaling pathway, and that ferroptosis may act as an initiator or intermediate mediator leading to AIH.\n                  <\/jats:p>","DOI":"10.1155\/2021\/6551069","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T23:50:08Z","timestamp":1640044208000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["GPX4\u2010Regulated Ferroptosis Mediates S100\u2010Induced Experimental Autoimmune Hepatitis Associated with the Nrf2\/HO\u20101 Signaling 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