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http://hdl.handle.net/1942/25853
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DC Field | Value | Language |
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dc.contributor.author | Vancamelbeke, Maaike | - |
dc.contributor.author | Vanuytsel, Tim | - |
dc.contributor.author | Farre, Ricard | - |
dc.contributor.author | Verstockt, Sare | - |
dc.contributor.author | Ferrante, Marc | - |
dc.contributor.author | Van Assche, Gert | - |
dc.contributor.author | Rutgeerts, Paul | - |
dc.contributor.author | Schuit, Frans | - |
dc.contributor.author | Vermeire, Severine | - |
dc.contributor.author | ARIJS, Ingrid | - |
dc.contributor.author | Cleynen, Isabelle | - |
dc.date.accessioned | 2018-04-12T08:43:14Z | - |
dc.date.available | 2018-04-12T08:43:14Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | INFLAMMATORY BOWEL DISEASES, 23(10), p. 1718-1729 | - |
dc.identifier.issn | 1078-0998 | - |
dc.identifier.uri | http://hdl.handle.net/1942/25853 | - |
dc.description.abstract | Background: Intestinal barrier defects are common in patients with inflammatory bowel disease (IBD). To identify which components could underlie these changes, we performed an in-depth analysis of epithelial barrier genes in IBD. Methods: A set of 128 intestinal barrier genes was selected. Polygenic risk scores were generated based on selected barrier gene variants that were associated with Crohn's disease (CD) or ulcerative colitis (UC) in our study. Gene expression was analyzed using microarray and quantitative reverse transcription polymerase chain reaction. Influence of barrier gene variants on expression was studied by cis-expression quantitative trait loci mapping and comparing patients with low-and high-risk scores. Results: Barrier risk scores were significantly higher in patients with IBD than controls. At single-gene level, the associated barrier single-nucleotide polymorphisms were most significantly enriched in PTGER4 for CD and HNF4A for UC. As a group, the regulating proteins were most enriched for CD and UC. Expression analysis showed that many epithelial barrier genes were significantly dysregulated in active CD and UC, with overrepresentation of mucus layer genes. In uninflamed CD ileum and IBD colon, most barrier gene levels restored to normal, except for MUC1 and MUC4 that remained persistently increased compared with controls. Expression levels did not depend on cis-regulatory variants nor combined genetic risk. Conclusions: We found genetic and transcriptomic dysregulations of key epithelial barrier genes and components in IBD. Of these, we believe that mucus genes, in particular MUC1 and MUC4, play an essential role in the pathogenesis of IBD and could represent interesting targets for treatment. | - |
dc.description.sponsorship | This work was supported by the Research Foundation Flanders (FWO) [G.0440.06, G.0479.10] and the European Crohn's and Colitis Organisation [ECCO Grant 2013]. T. Vanuytsel, M. Ferrante, G. Van Assche, and S. Vermeire are senior clinical investigators of the FWO. T. Vanuytsel receives lecture fees from Will Pharma and consulting fees from Shire. M. Ferrante reports financial support for research from Takeda; lecture fees from Abbvie, Boehringer-Ingelheim, Chiesi, Falk, Ferring, Janssen, Mitsubishi Tanabe, MSD, Takeda, Tillotts, and Zeria; and consulting fees from Abbvie, Boehringer-Ingelheim, Ferring, Janssen, and MSD. G. Van Assche receives support for research from Abbvie and MSD; lecture fees from Abbvie, MSD, Ferring, Janssen, and Takeda; and consulting fees from Abbvie, MSD, and Takeda. P. Rutgeerts receives research support and lecture fees from Abbvie, Centocor, and Merck; and consulting fees from Abbvie, Centocor, Merck, UCB, Takeda, Genentech/Hoffman-LaRoche, Serono, Bristol Myers Squibb, Robarts, Tillotts, Pfizer, and Falk Pharma. S. Vermeire reports grant support from Abbvie, MSD, and Takeda; lecture fees from Abbvie, MSD, Takeda, Ferring, Falk Pharma, Hospira, and Tillotts; and consulting fees from Abbvie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer, Galapagos, Mundipharma, Hospira, Celgene, Second Genome, and Janssen. The remaining authors have no conflict of interest to disclose. I. Arijs and I. Cleynen share last co-authorship. | - |
dc.language.iso | en | - |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | - |
dc.rights | 2017 Crohn’s & Colitis Foundation. Unauthorized reproduction of this article is prohibited. | - |
dc.subject.other | intestinal barrier | - |
dc.subject.other | genetic analysis | - |
dc.subject.other | inflammatory bowel disease | - |
dc.subject.other | mucosal gene expression | - |
dc.title | Genetic and Transcriptomic Bases of Intestinal Epithelial Barrier Dysfunction in Inflammatory Bowel Disease | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 1729 | - |
dc.identifier.issue | 10 | - |
dc.identifier.spage | 1718 | - |
dc.identifier.volume | 23 | - |
local.format.pages | 12 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | [Vancamelbeke, Maaike; Vanuytsel, Tim; Farre, Ricard; Ferrante, Marc; Van Assche, Gert; Rutgeerts, Paul; Vermeire, Severine; Arijs, Ingrid] Katholieke Univ Leuven, Dept Clin & Expt Med, Translat Res Ctr Gastrointestinal Disorders TARGI, Leuven, Belgium. [Vanuytsel, Tim; Ferrante, Marc; Van Assche, Gert; Rutgeerts, Paul; Vermeire, Severine] Univ Hosp Leuven, Dept Gastroenterol & Hepatol, Leuven, Belgium. [Verstockt, Sare; Cleynen, Isabelle] Katholieke Univ Leuven, Dept Human Genet, Lab Complex Genet, O&N1 Herestr 49,Box 607, B-3000 Leuven, Belgium. [Schuit, Frans] Katholieke Univ Leuven, Dept Cellular & Mol Med, Gene Express Unit, Leuven, Belgium. [Arijs, Ingrid] Hasselt Univ, Fac Med & Life Sci, Hasselt, Belgium. [Arijs, Ingrid] Jessa Hosp, Hasselt, Belgium. | - |
local.publisher.place | PHILADELPHIA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1097/MIB.0000000000001246 | - |
dc.identifier.pmid | 28885228 | - |
dc.identifier.isi | 000412445300012 | - |
dc.identifier.eissn | 1536-4844 | - |
local.provider.type | PubMed | - |
local.uhasselt.international | no | - |
item.accessRights | Restricted Access | - |
item.fulltext | With Fulltext | - |
item.fullcitation | Vancamelbeke, Maaike; Vanuytsel, Tim; Farre, Ricard; Verstockt, Sare; Ferrante, Marc; Van Assche, Gert; Rutgeerts, Paul; Schuit, Frans; Vermeire, Severine; ARIJS, Ingrid & Cleynen, Isabelle (2017) Genetic and Transcriptomic Bases of Intestinal Epithelial Barrier Dysfunction in Inflammatory Bowel Disease. In: INFLAMMATORY BOWEL DISEASES, 23(10), p. 1718-1729. | - |
item.contributor | Vancamelbeke, Maaike | - |
item.contributor | Vanuytsel, Tim | - |
item.contributor | Farre, Ricard | - |
item.contributor | Verstockt, Sare | - |
item.contributor | Ferrante, Marc | - |
item.contributor | Van Assche, Gert | - |
item.contributor | Rutgeerts, Paul | - |
item.contributor | Schuit, Frans | - |
item.contributor | Vermeire, Severine | - |
item.contributor | ARIJS, Ingrid | - |
item.contributor | Cleynen, Isabelle | - |
crisitem.journal.issn | 1078-0998 | - |
crisitem.journal.eissn | 1536-4844 | - |
Appears in Collections: | Research publications |
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IBD-D-16-00115 1718..1729.pdf Restricted Access | Published version | 683.31 kB | Adobe PDF | View/Open Request a copy |
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