{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:00:11Z","timestamp":1792821611617,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300594"],"award-info":[{"award-number":["82300594"]}],"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":["82270595"],"award-info":[{"award-number":["82270595"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institutional Foundation of The First Affiliated Hospital of Xi\u2019an Jiaotong University","award":["2022QN-07"],"award-info":[{"award-number":["2022QN-07"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Impaired intestinal epithelial barrier has been considered to be associated with an increasing variety of gastrointestinal diseases, especially inflammatory bowel disease (IBD) encompassing Crohn\u2019s disease (CD) and ulcerative colitis (UC). We aimed to investigate the role of Gasdermin B (GSDMB) in modulating intestinal epithelial barrier integrity and proposed a promising therapeutic strategy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Gasdermin B expression was evaluated in adult CD samples by molecular biology means and single-cell transcriptomes. We generated GSDMB (Rosa26-lsl\/lsl-GSDMB;Villin-Cre) and one of its functional missense variant rs2305480 (Rosa26-lsl\/lsl-GSDMB-MU;Villin-Cre) intestinal epithelial-specific knock in mice to observe the functions of GSDMB in intestinal epithelial barrier. RNA-seq analysis as well as human and murine intestine-derived organoids were used to determine the pathogenic mechanism of GSDMB.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The expression of GSDMB was increased during active intestinal inflammation and principally localized in intestinal epithelial cells (IECs). Rosa26-lsl\/lsl-GSDMB;Villin-Cre mice developed enterocolitis and exhibited aberrant intestinal barrier integrity. Mechanistically, epithelial GSDMB modulated hyperactive unfolded protein response of IECs by up-regulating BHLHA15 to mediate intestinal barrier injury. Rosa26-lsl\/lsl-GSDMB-MU;Villin-Cre mice with the mutant rs2305480 of GSDMB aggravated such inflammatory effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We have uncovered an important and previously unrecognized role of GSDMB in intestinal homeostasis, which represents a potential therapeutic target for intestinal inflammation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaf012","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T12:53:33Z","timestamp":1737377613000},"source":"Crossref","is-referenced-by-count":4,"title":["Gasdermin B modulates intestinal epithelial homeostasis via regulating hyperactive unfolded protein response in Crohn\u2019s disease"],"prefix":"10.1093","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1699-9213","authenticated-orcid":false,"given":"Wenbin","family":"Gong","sequence":"first","affiliation":[{"name":"Department of General Surgery, The First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an 710061 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peizhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical School of Nanjing University, Department of General Surgery, Jinling Hospital , Nanjing 210002 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanhan","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical School of Nanjing University, Department of General Surgery, Jinling Hospital , Nanjing 210002 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangguang","family":"Li","sequence":"additional","affiliation":[{"name":"Medical School of Nanjing University, Department of General Surgery, Jinling Hospital , Nanjing 210002 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University , Nanjing 210019 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhen","family":"Li","sequence":"additional","affiliation":[{"name":"Medical School of Nanjing University, Department of General Surgery, Jinling Hospital , Nanjing 210002 ,","place":["China"]},{"name":"The Affiliated Hospital of Qingdao University , Qingdao 266000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Kang","sequence":"additional","affiliation":[{"name":"Medical School of Nanjing University, Department of General Surgery, Jinling Hospital , Nanjing 210002 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Jiao","sequence":"additional","affiliation":[{"name":"BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University , Nanjing 210019 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Medical School of Nanjing University, Department of General Surgery, Jinling Hospital , Nanjing 210002 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhao","sequence":"additional","affiliation":[{"name":"BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University , Nanjing 210019 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4697-4762","authenticated-orcid":false,"given":"Jianan","family":"Ren","sequence":"additional","affiliation":[{"name":"Medical School of Nanjing University, Department of General Surgery, Jinling Hospital , Nanjing 210002 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"2025021413121610900_CIT0001","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrgastro.2016.169","article-title":"The intestinal epithelial barrier: a therapeutic target","volume":"14","author":"Odenwald","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol."},{"key":"2025021413121610900_CIT0002","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: regulators of barrier function and 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