{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:51:50Z","timestamp":1790794310183,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160135"],"award-info":[{"award-number":["82160135"]}],"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":["82360146"],"award-info":[{"award-number":["82360146"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to elucidate whether NCOA4\u2010mediated ferritinophagy promotes ferroptosis and contributes to renal tubulointerstitial fibrosis, and to clarify its interaction with the Nrf2 antioxidant pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A uric acid (UA)\u2010induced ferroptosis model was established in HK\u20102 cells and a hyperuricemic nephropathy (HN) model was constructed in C57BL\/6 mice using adenine and potassium oxonate gavage. NCOA4 and Nrf2 were silenced by shRNA in\u00a0vitro and AAV9\u2010mediated knockdown in\u00a0vivo. Ferroptosis, oxidative stress and fibrosis were evaluated using qRT\u2010PCR, western blotting, immunofluorescence, biochemical assays and histopathological staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      UA exposure significantly increased NCOA4 expression, promoted ferritin degradation, and triggered iron accumulation, lipid peroxidation, and suppression of the Nrf2\/GPX4\/SLC7A11 axis. NCOA4 knockdown increased antioxidant defences, reduced Fe\n                      <jats:sup>2+<\/jats:sup>\n                      and ROS levels and alleviated \u03b1\u2010SMA and collagen IV expression in both HK\u20102 cells and HN mice. However, co\u2010silencing Nrf2 abolished these protective effects, indicating functional coupling between NCOA4 and Nrf2 signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NCOA4\u2010mediated ferritinophagy acts as an upstream driver of ferroptosis and tubulointerstitial fibrosis in hyperuricemia\u2010associated CKD. The NCOA4\/Nrf2 axis represents a mechanistic link and potential therapeutic target for preventing renal fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nep.70228","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:51:33Z","timestamp":1782089493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>NCOA4<\/scp>\n                    \u2010Mediated Ferroptosis Drives Tubulointerstitial Fibrosis in Hyperuricemia\u2010Associated Chronic Kidney Disease"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3005-0693","authenticated-orcid":false,"given":"Minhui","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nephrology Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University)  Haikou Hainan 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