{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:30:05Z","timestamp":1788510605376,"version":"build-2803163510"},"reference-count":46,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,1,21]],"date-time":"2027-01-21T00:00:00Z","timestamp":1800489600000},"content-version":"am","delay-in-days":354,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100006823","name":"Boston Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK061931"],"award-info":[{"award-number":["R01DK061931"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK068271"],"award-info":[{"award-number":["R01DK068271"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK034854"],"award-info":[{"award-number":["P30DK034854"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["li.uscap.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Laboratory Investigation"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.labinv.2025.104271","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T07:51:43Z","timestamp":1765525903000},"page":"104271","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tight Junction Defects in Aganglionic and Ganglionic Colon in Children With Hirschsprung Disease"],"prefix":"10.1016","volume":"106","author":[{"given":"Lorena","family":"Rincon-Cruz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-9116","authenticated-orcid":false,"given":"Leah","family":"Froehle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabnam","family":"Abhati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Goldsmith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0627-9455","authenticated-orcid":false,"given":"Jerrold","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2475-2699","authenticated-orcid":false,"given":"Prathima","family":"Nandivada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.labinv.2025.104271_bib1","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.917243","article-title":"Ednrb-\/- mice with hirschsprung disease are missing Gad2-expressing enteric neurons in the ganglionated small intestine","volume":"10","author":"Bhave","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"10.1016\/j.labinv.2025.104271_bib2","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/wdev.57","article-title":"Hirschsprung disease: a developmental disorder of the enteric nervous system","volume":"2","author":"McKeown","year":"2013","journal-title":"Wiley Interdiscip Rev Dev Biol"},{"issue":"3","key":"10.1016\/j.labinv.2025.104271_bib3","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1097\/MOP.0000000000000210","article-title":"Hirschsprung\u2019s associated enterocolitis","volume":"27","author":"Gosain","year":"2015","journal-title":"Curr Opin Pediatr"},{"issue":"9","key":"10.1016\/j.labinv.2025.104271_bib4","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.jpedsurg.2021.03.046","article-title":"Management and outcomes for long-segment Hirschsprung disease: a systematic review from the APSA Outcomes and Evidence Based Practice Committee","volume":"56","author":"Kawaguchi","year":"2021","journal-title":"J Pediatr Surg"},{"issue":"1","key":"10.1016\/j.labinv.2025.104271_bib5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12893-018-0383-6","article-title":"Surgical treatment of children with total colonic aganglionosis: functional and metabolic long-term outcome","volume":"18","author":"Urla","year":"2018","journal-title":"BMC Surg"},{"issue":"2","key":"10.1016\/j.labinv.2025.104271_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.sempedsurg.2022.151157","article-title":"The science of Hirschsprung disease: what we know and where we are headed","volume":"31","author":"Mueller","year":"2022","journal-title":"Semin Pediatr Surg"},{"issue":"1","key":"10.1016\/j.labinv.2025.104271_bib7","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41598-018-36967-z","article-title":"Gut microbiota-mediated gene-environment interaction in the TashT mouse model of Hirschsprung disease","volume":"9","author":"Tour\u00e9","year":"2019","journal-title":"Sci Rep"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0128822","article-title":"Impaired cellular immunity in the murine neural crest conditional deletion of endothelin receptor-B model of Hirschsprung\u2019s disease","volume":"10","author":"Gosain","year":"2015","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.labinv.2025.104271_bib9","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-78340-z","article-title":"Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung\u2019s disease","volume":"10","author":"Dariel","year":"2020","journal-title":"Sci Rep"},{"issue":"8","key":"10.1016\/j.labinv.2025.104271_bib10","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1136\/gutjnl-2022-328421","article-title":"Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn\u2019s disease highlight earliest events of pathogenesis","volume":"72","author":"Leibovitzh","year":"2023","journal-title":"Gut"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib11","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1053\/j.gastro.2021.08.047","article-title":"The tight junction protein ZO-1 is dispensable for barrier function but critical for effective mucosal repair","volume":"161","author":"Kuo","year":"2021","journal-title":"Gastroenterology"},{"issue":"4","key":"10.1016\/j.labinv.2025.104271_bib12","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.cell.2006.06.043","article-title":"ZO-1 and ZO-2 independently determine where claudins are polymerized in tight-junction strand formation","volume":"126","author":"Umeda","year":"2006","journal-title":"Cell"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib13","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1083\/jcb.124.6.949","article-title":"Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein","volume":"124","author":"Jesaitis","year":"1994","journal-title":"J Cell Biol"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib14","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1053\/j.gastro.2020.08.005","article-title":"Increased intestinal permeability is associated with later development of Crohn\u2019s disease","volume":"159","author":"Turpin","year":"2020","journal-title":"Gastroenterology"},{"issue":"8","key":"10.1016\/j.labinv.2025.104271_bib15","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1136\/gutjnl-2011-300695","article-title":"Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease","volume":"61","author":"Kiesslich","year":"2012","journal-title":"Gut"},{"issue":"10","key":"10.1016\/j.labinv.2025.104271_bib16","doi-asserted-by":"crossref","first-page":"5197","DOI":"10.1172\/JCI138697","article-title":"Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice","volume":"130","author":"Raju","year":"2020","journal-title":"J Clin Invest"},{"issue":"4","key":"10.1016\/j.labinv.2025.104271_bib17","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/s41591-019-0393-7","article-title":"Intracellular MLCK1 diversion reverses barrier loss to restore mucosal homeostasis","volume":"25","author":"Graham","year":"2019","journal-title":"Nat Med"},{"issue":"2","key":"10.1016\/j.labinv.2025.104271_bib18","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.gastro.2005.05.002","article-title":"Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution","volume":"129","author":"Heller","year":"2005","journal-title":"Gastroenterology"},{"issue":"22","key":"10.1016\/j.labinv.2025.104271_bib19","doi-asserted-by":"crossref","first-page":"5597","DOI":"10.3390\/ijms20225597","article-title":"Celiac disease monocytes induce a barrier defect in intestinal epithelial cells","volume":"20","author":"Delbue","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"12","key":"10.1016\/j.labinv.2025.104271_bib20","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1038\/ajg.2011.257","article-title":"The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype","volume":"106","author":"Bertiaux-Vanda\u00eble","year":"2011","journal-title":"Am J Gastroenterol"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib21","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/ajg.2017.48","article-title":"Constipation-predominant irritable bowel syndrome females have normal colonic barrier and secretory function","volume":"112","author":"Peters","year":"2017","journal-title":"Am J Gastroenterol"},{"issue":"2","key":"10.1016\/j.labinv.2025.104271_bib22","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3390\/cells12020236","article-title":"Impaired intestinal permeability of tricellular tight junctions in patients with irritable bowel syndrome with mixed bowel habits (IBS-M)","volume":"12","author":"Awad","year":"2023","journal-title":"Cells"},{"issue":"243","key":"10.1016\/j.labinv.2025.104271_bib23","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3008941","article-title":"Recipient NK cell inactivation and intestinal barrier loss are required for MHC-matched graft-versus-host disease","volume":"6","author":"Nalle","year":"2014","journal-title":"Sci Transl Med"},{"issue":"2","key":"10.1016\/j.labinv.2025.104271_bib24","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1172\/JCI98554","article-title":"Graft-versus-host disease propagation depends on increased intestinal epithelial tight junction permeability","volume":"129","author":"Nalle","year":"2019","journal-title":"J Clin Invest"},{"issue":"4","key":"10.1016\/j.labinv.2025.104271_bib25","doi-asserted-by":"crossref","DOI":"10.1002\/cpz1.68","article-title":"A simple method for creating a high-content microscope for imaging multiplexed tissue microarrays","volume":"1","author":"Abtahi","year":"2021","journal-title":"Curr Protoc"},{"issue":"1","key":"10.1016\/j.labinv.2025.104271_bib26","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1177\/1093526619890735","article-title":"Postoperative pullthrough obstruction in Hirschsprung disease: etiologies and diagnosis","volume":"23","author":"Kapur","year":"2020","journal-title":"Pediatr Dev Pathol"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0099944","article-title":"Altered goblet cell differentiation and surface mucus properties in Hirschsprung disease","volume":"9","author":"Thiagarajah","year":"2014","journal-title":"PLoS One"},{"issue":"2","key":"10.1016\/j.labinv.2025.104271_bib28","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a002584","article-title":"Physiology and function of the tight junction","volume":"1","author":"Anderson","year":"2009","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"7","key":"10.1016\/j.labinv.2025.104271_bib29","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41575-023-00766-3","article-title":"Paracellular permeability and tight junction regulation in gut health and disease","volume":"20","author":"Horowitz","year":"2023","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"11","key":"10.1016\/j.labinv.2025.104271_bib30","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib31","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.modgep.2005.12.001","article-title":"Claudin profiling in the mouse during postnatal intestinal development and along the gastrointestinal tract reveals complex expression patterns","volume":"6","author":"Holmes","year":"2006","journal-title":"Gene Expr Patterns"},{"issue":"3","key":"10.1016\/j.labinv.2025.104271_bib32","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1053\/j.gastro.2010.08.006","article-title":"Loss of claudin-15, but not claudin-2, causes Na+ deficiency and glucose malabsorption in mouse small intestine","volume":"140","author":"Tamura","year":"2011","journal-title":"Gastroenterology"},{"issue":"1","key":"10.1016\/j.labinv.2025.104271_bib33","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.yexcr.2017.03.036","article-title":"Contributions of intestinal epithelial barriers to health and disease","volume":"358","author":"Choi","year":"2017","journal-title":"Exp Cell Res"},{"issue":"2","key":"10.1016\/j.labinv.2025.104271_bib34","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1053\/j.gastro.2007.11.040","article-title":"Megaintestine in claudin-15-deficient mice","volume":"134","author":"Tamura","year":"2008","journal-title":"Gastroenterology"},{"issue":"2","key":"10.1016\/j.labinv.2025.104271_bib35","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jpedsurg.2020.06.018","article-title":"A piglet model of iatrogenic rectosigmoid hypoganglionosis reveals the impact of the enteric nervous system on gut barrier function and microbiota postnatal development","volume":"56","author":"Arnaud","year":"2021","journal-title":"J Pediatr Surg"},{"issue":"1","key":"10.1016\/j.labinv.2025.104271_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1247\/csf.22068","article-title":"Reconstitution of functional tight junctions with individual claudin subtypes in epithelial cells","volume":"48","author":"Furuse","year":"2023","journal-title":"Cell Struct Funct"},{"issue":"1","key":"10.1016\/j.labinv.2025.104271_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.jpedsurg.2024.161900","article-title":"Impact of epithelial claudin-4 and leukotriene B4 receptor 2 in normoganglionic Hirschsprung disease colon on post pull-through enterocolitis","volume":"60","author":"Abe","year":"2025","journal-title":"J Pediatr Surg"},{"issue":"1","key":"10.1016\/j.labinv.2025.104271_bib38","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.1038\/s41467-022-31587-8","article-title":"Tight junction channel regulation by interclaudin interference","volume":"13","author":"Shashikanth","year":"2022","journal-title":"Nat Commun"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib39","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.chom.2017.05.009","article-title":"IL-22 upregulates epithelial claudin-2 to drive diarrhea and enteric pathogen clearance","volume":"21","author":"Tsai","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"16","key":"10.1016\/j.labinv.2025.104271_bib40","doi-asserted-by":"crossref","first-page":"12037","DOI":"10.1074\/jbc.M109.064808","article-title":"Epithelial myosin light chain kinase activation induces mucosal interleukin-13 expression to alter tight junction ion selectivity","volume":"285","author":"Weber","year":"2010","journal-title":"J Biol Chem"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib41","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1038\/mi.2014.21","article-title":"Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis","volume":"7","author":"Ahmad","year":"2014","journal-title":"Mucosal Immunol"},{"issue":"10","key":"10.1016\/j.labinv.2025.104271_bib42","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2217877121","article-title":"Claudin-2 upregulation enhances intestinal permeability, immune activation, dysbiosis, and mortality in sepsis","volume":"121","author":"Oami","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"10.1016\/j.labinv.2025.104271_bib43","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.4049\/jimmunol.1700105","article-title":"Microbial-derived butyrate promotes epithelial barrier function through IL-10 receptor-dependent repression of claudin-2","volume":"199","author":"Zheng","year":"2017","journal-title":"J Immunol"},{"issue":"5","key":"10.1016\/j.labinv.2025.104271_bib44","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1053\/j.gastro.2019.07.058","article-title":"Inflammation-induced occludin downregulation limits epithelial apoptosis by suppressing caspase-3 expression","volume":"157","author":"Kuo","year":"2019","journal-title":"Gastroenterology"},{"issue":"4","key":"10.1016\/j.labinv.2025.104271_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.labinv.2022.100036","article-title":"Intestinal epithelial digestive, transport, and barrier protein expression is increased in environmental enteric dysfunction","volume":"103","author":"Abtahi","year":"2023","journal-title":"Lab Invest"},{"issue":"6","key":"10.1016\/j.labinv.2025.104271_bib46","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1053\/j.gastro.2021.01.221","article-title":"Mucosal genomics implicate lymphocyte activation and lipid metabolism in refractory environmental enteric dysfunction","volume":"160","author":"Haberman","year":"2021","journal-title":"Gastroenterology"}],"container-title":["Laboratory Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683725001825?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683725001825?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T07:13:30Z","timestamp":1783667610000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0023683725001825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["S0023683725001825"],"URL":"https:\/\/doi.org\/10.1016\/j.labinv.2025.104271","relation":{},"ISSN":["0023-6837"],"issn-type":[{"value":"0023-6837","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Tight Junction Defects in Aganglionic and Ganglionic Colon in Children With Hirschsprung Disease","name":"articletitle","label":"Article Title"},{"value":"Laboratory Investigation","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.labinv.2025.104271","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"104271"}}