{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:19:08Z","timestamp":1792383548809,"version":"4.4.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":76,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017695","name":"Health Commission of Hunan Province","doi-asserted-by":"publisher","award":["20201399"],"award-info":[{"award-number":["20201399"]}],"id":[{"id":"10.13039\/100017695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gasdermin E (GSDME) is a newly identified pyroptosis executioner and is upregulated in the intestinal epithelial cell (IEC) of ulcerative colitis (UC) patients. However, the effects of epithelial GSDME on UC remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bone marrow chimera experiments were performed to investigate the role of GSDME in nonhematopoietic cells, mainly including IECs. An FITC-dextran assay was used to assess the integrity of the intestinal epithelial barrier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gsdme\u2013\/\u2013 chimeras that were reconstituted with wild-type bone marrow cells exhibited lower weight loss, disease activity index, colon shortening, and histology scores than wild-type chimeras after treatment with dextran sulfate sodium (DSS). However, Gsdme+\/+ chimeras that were reconstituted with Gsdme-deficient bone marrow cells were not protected from DSS-induced colitis compared with wild-type chimeras. Importantly, DSS treatment activated Caspase-3 and cleaved GSDME to generate GSDME-N terminal fragments that are responsible for the induction of pyroptosis in IECs, but not in the intestinal lamina propria cell. Additionally, GSDME deficiency inhibited DSS-induced disruption of the intestinal epithelial barrier. Mechanistically, GSDME-mediated IEC pyroptosis is dependent on Caspase-3 activation, which is supported by the observation that the Caspase-3 inhibitor Z-DEVD-FMK inhibited DSS-induced GSDME cleavage in IECs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We show that GSDME-mediated epithelial pyroptosis contributes to the development of DSS-induced colitis by promoting intestinal inflammation and disrupting the intestinal epithelial barrier.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/gastro\/goaf021","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T23:19:15Z","timestamp":1739834355000},"source":"Crossref","is-referenced-by-count":12,"title":["Gasdermin E-mediated intestinal epithelial pyroptosis promotes chemically induced colitis in mice"],"prefix":"10.1093","volume":"13","author":[{"given":"Yi-Zhong","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hunan Provincial People\u2019s Hospital and The First Affiliated Hospital of Hunan Normal University , Changsha, Hunan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xie","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Hengyang Medical School, University of South China , Hengyang, Hunan,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"The First People's Hospital of Xiangtan City , Xiangtan, Hunan,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hunan Provincial People\u2019s Hospital and The First Affiliated Hospital of Hunan Normal University , Changsha, Hunan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Qi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hunan Provincial People\u2019s Hospital and The First Affiliated Hospital of Hunan Normal University , Changsha, Hunan, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hunan Provincial People\u2019s Hospital and The First Affiliated Hospital of Hunan Normal University , Changsha, Hunan, P. 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