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Bispebjerg Hospital - a part of Copenhagen University Hospital
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Altered Structural Expression and Enzymatic Activity Parameters in Quiescent Ulcerative Colitis: Are These Potential Normalization Criteria?

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  • Sebastian Kjærgaard
  • Morten M B Damm
  • Joan Chang
  • Lene B Riis
  • Hanne B Rasmussen
  • Rasmus Hytting-Andreasen
  • Susanne M Krug
  • Jörg-Dieter Schulzke
  • Niels Bindslev
  • Mark Berner Hansen
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Mucosal healing determined by endoscopy is currently the remission standard for ulcerative colitis (UC). However, new criteria for remission are emerging, such as histologic normalization, which appears to correlate better to the risk of relapse. Here, we study mucosal healing on a molecular and functional level in quiescent UC. We obtained endoscopic biopsies from 33 quiescent UC patients and from 17 controls. Histology was assessed using Geboes score. Protein and mRNA levels were evaluated for the tight junction proteins claudin-2, claudin-4, occludin, and tricellulin, as well as Cl-/HCO3- exchanger DRA, and cyclo-oxygenase enzymes (COX-1, COX-2). The mucosal activity of COX-1 and COX-2 enzymes was assessed in modified Ussing chambers, measuring electrogenic ion transport (short-circuit current, SCC). Chronic inflammation was present in most UC patients. The protein level of claudin-4 was reduced, while mRNA-levels of claudin-2 and claudin-4 were upregulated in UC patients. Surprisingly, the mRNA level of COX-1 was downregulated, but was unaltered for COX-2. Basal ion transport was not affected, while COX-2 inhibition induced a two-fold larger decrease in SCC in UC patients. Despite being in clinical and endoscopic remission, quiescent UC patients demonstrated abnormal mucosal barrier properties at the molecular and functional level. Further exploration of mucosal molecular signature for revision of current remission standards should be considered.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume21
Issue number5
ISSN1661-6596
DOIs
Publication statusPublished - 10 Mar 2020

    Research areas

  • Adult, Aged, Biopsy, Case-Control Studies, Claudin-1/genetics, Claudins/genetics, Colitis, Ulcerative/genetics, Cyclooxygenase 1/genetics, Cyclooxygenase 2/genetics, Female, Gene Expression Regulation, Gene Regulatory Networks, Humans, MARVEL Domain Containing 2 Protein/genetics, Male, Middle Aged, Young Adult

ID: 62408280