{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:02:51Z","timestamp":1792803771559,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T00:00:00Z","timestamp":1582502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Children\u2019s Memorial Health Institute","award":["236\/15"],"award-info":[{"award-number":["236\/15"]}],"id":[{"id":"https:\/\/ror.org\/020atbp69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The Children\u2019s Memorial Health Institute","award":["S147\/2016"],"award-info":[{"award-number":["S147\/2016"]}],"id":[{"id":"https:\/\/ror.org\/020atbp69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The Children\u2019s Memorial Health Institute","award":["S156\/2017"],"award-info":[{"award-number":["S156\/2017"]}],"id":[{"id":"https:\/\/ror.org\/020atbp69","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Disruption of epithelial junctional complex (EJC), especially tight junctions (TJ), resulting in increased intestinal permeability, is supposed to activate the enhanced immune response to gluten and to induce the development of celiac disease (CD). This study is aimed to present the role of EJC in CD pathogenesis. To analyze differentially expressed genes the next-generation mRNA sequencing data from CD326+ epithelial cells isolated from non-celiac and celiac patients were involved. Ultrastructural studies with morphometry of EJC were done in potential CD, newly recognized active CD, and non-celiac controls. The transcriptional analysis suggested disturbances of epithelium and the most significant gene ontology enriched terms in epithelial cells from CD patients related to the plasma membrane, extracellular exome, extracellular region, and extracellular space. Ultrastructural analyses showed significantly tighter TJ, anomalies in desmosomes, dilatations of intercellular space, and shorter microvilli in potential and active CD compared to controls. Enterocytes of fetal-like type and significantly wider adherence junctions were observed only in active CD. In conclusion, the results do not support the hypothesis that an increased passage of gluten peptides by unsealing TJ precedes CD development. However, increased intestinal permeability due to abnormality of epithelium might play a role in CD onset.<\/jats:p>","DOI":"10.3390\/cells9020516","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T04:21:26Z","timestamp":1582604486000},"page":"516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Transcriptional and Ultrastructural Analyses Suggest Novel Insights into Epithelial Barrier Impairment in Celiac Disease"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-2340","authenticated-orcid":false,"given":"Agnieszka","family":"Sowi\u0144ska","sequence":"first","affiliation":[{"name":"Department of Pathology, The Children Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8234-1877","authenticated-orcid":false,"given":"Yasser","family":"Morsy","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Z\u00fcrich, CH-8001 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Czarnowska","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Children Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Oralewska","sequence":"additional","affiliation":[{"name":"Clinic of Gastroenterology, The Children Memorial Health Institute, Al. 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Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00251-012-0599-z","article-title":"Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules","volume":"64","author":"Sollid","year":"2012","journal-title":"Immunogenetics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1053\/j.gastro.2015.01.030","article-title":"Local communication among mucosal immune cells in patients with celiac disease","volume":"148","author":"Mulder","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7505","DOI":"10.3748\/wjg.v23.i42.7505","article-title":"Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota\u2013Key players in the pathogenesis of celiac disease","volume":"23","author":"Cukrowska","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1007\/s10620-019-05646-y","article-title":"Breaking down barriers: How understanding celiac disease pathogenesis informed the development of novel treatments","volume":"64","author":"Valitutti","year":"2019","journal-title":"Dig. Dis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/S0140-6736(00)02169-3","article-title":"Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease","volume":"355","author":"Fasano","year":"2000","journal-title":"Lancet"},{"key":"ref_7","first-page":"1607","article-title":"Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure","volume":"123","author":"Panigrahi","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1053\/j.gastro.2008.03.023","article-title":"Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3","volume":"135","author":"Lammers","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1136\/gut.52.2.218","article-title":"Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function","volume":"52","author":"Clemente","year":"2003","journal-title":"Gut"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00428-009-0879-7","article-title":"Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum in children with celiac disease","volume":"456","author":"Gyorffy","year":"2010","journal-title":"Virchows Arch."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1309\/DTYRA91G8R0KTM8M","article-title":"Altered expression, localization, and phosphorylation of epithelial junctional proteins in celiac disease","volume":"125","author":"Ciccocioppo","year":"2006","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s00428-014-1651-1","article-title":"Are alternations of tight junctions at molecular and ultrastructural level different in duodenal biopsies of patients with celiac disease and Crohn\u2019s disease?","volume":"465","author":"Goswami","year":"2014","journal-title":"Virchows Arch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1097\/MCG.0000000000000436","article-title":"Structural and functional changes in the tight junctions of asymptomatic and serology-negative first-degree relatives of patients with celiac disease","volume":"50","author":"Mishra","year":"2016","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation","volume":"40","author":"McCarthy","year":"2012","journal-title":"Nucleic. Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gkn923","article-title":"Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists","volume":"37","author":"Huang","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1097\/00042737-199910000-00019","article-title":"The histopathology of celiac disease: Time for a standardized report scheme for pathologists","volume":"11","author":"Oberhuber","year":"1999","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/MPG.0b013e31821a23d0","article-title":"ESPGHAN Working Group on Coeliac Disease Diagnosis; ESPGHAN Gastroenterology Committee; European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease","volume":"54","author":"Husby","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_20","first-page":"269","article-title":"Transmission electron microscopy of microvilli of intestinal epithelial cells in celiac disease in remission and transient gluten enteropathy in children after a gluten-free diet","volume":"16","author":"Dyduch","year":"1993","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_21","first-page":"87","article-title":"Gradual disappearance of vacuolated enterocytes in the small intestine of neonatal piglets","volume":"58","author":"Skrzypek","year":"2007","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.vetimm.2007.03.001","article-title":"Transmission of antibodies from mother to young: Evolutionary strategies in a proteolytic environment","volume":"117","author":"Baintner","year":"2007","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.4049\/jimmunol.161.5.2561","article-title":"The influence of mast cells on pathways of transepithelial antigen transport in rat intestine","volume":"161","author":"Berin","year":"1998","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S0002-9440(10)63308-1","article-title":"Antigen transport and cytoskeletal characteristics of a distinct enterocyte population in inflammatory bowel diseases","volume":"165","author":"Kersting","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1172\/JCI9258","article-title":"Enhanced intestinal transepithelial antigen transport in allergic rats is mediated by IgE and CD23 (FcepsilonRII)","volume":"106","author":"Yang","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.dld.2015.11.007","article-title":"Prevalence of celiac disease among first-degree relatives of Indian celiac disease patients","volume":"48","author":"Mishra","year":"2016","journal-title":"Dig. Liver. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1053\/j.gastro.2019.04.004","article-title":"Progression of celiac disease in children with antibodies against tissue transglutaminase and normal duodenal architecture","volume":"157","author":"Auricchio","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/cmi.2015.09","article-title":"Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization","volume":"13","author":"Kozakova","year":"2016","journal-title":"Cell Mol. Immunol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/2\/516\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:01:18Z","timestamp":1760173278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/2\/516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,24]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["cells9020516"],"URL":"https:\/\/doi.org\/10.3390\/cells9020516","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,24]]}}}