{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:08:27Z","timestamp":1789549707003,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study investigated the roles and mechanism of the transcription factor KLF9 and its downstream target gene TXNRD2 in ulcerative colitis (UC). An in vitro inflammatory model was established by stimulating human normal colonic mucosal epithelial cells (NCM460) with LPS and ATP. KLF9 or TXNRD2 expression was knocked down using RNA interference, and rescue experiments were performed using the NLRP3\u2010specific agonist nigericin or by co\u2010transfection with si\u2010TXNRD2. A 3% DSS\u2010induced UC model was established in C57BL\/6 mice. Interventions were performed by tail vein injection of sh\u2010KLF9 adeno\u2010associated virus and\/or intraperitoneal injection of nigericin. In DSS\u2010induced UC mouse colon tissues and LPS\/ATP\u2010stimulated NCM460 cells, KLF9 was upregulated. KLF9 directly bound to the TXNRD2 promoter. Silencing KLF9 restored TXNRD2 expression, alleviated LPS\/ATP\u2010induced oxidative stress, decreased the accumulation of cytoplasmic ox\u2010mtDNA and mtDNA, and inhibited NLRP3 inflammasome activation, as well as reduced pyroptosis, LDH release, and pro\u2010inflammatory cytokine secretion. si\u2010TXNRD2 or nigericin partially reversed the protective effects of KLF9 silencing. Colon\u2010specific KLF9 knockdown improved DSS\u2010induced weight loss, colonic shortening, disease activity index, and histopathological damage in mice, while simultaneously upregulating TXNRD2, inhibiting the NLRP3 pathway, and reducing oxidative stress and cytoplasmic mtDNA accumulation. Nigericin intervention partially offset the protective effects of KLF9 knockdown. KLF9 suppresses TXNRD2 transcription, leading to increased mitochondrial oxidative stress and the release of ox\u2010mtDNA in intestinal epithelial cells, which in turn triggers NLRP3 inflammasome activation, driving pyroptosis and intestinal inflammation.<\/jats:p>","DOI":"10.1002\/jbt.71074","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:25:53Z","timestamp":1787567153000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulation of the KLF9\/TXNRD2 Axis Leads to Mitochondrial DNA Oxidation and NLRP3 Inflammasome Activation in Ulcerative Colitis"],"prefix":"10.1002","volume":"40","author":[{"given":"Yijia","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Jiaxing University Jiaxing City 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University Jiaxing City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junguo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Second Affiliated Hospital of Jiaxing University Jiaxing City 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