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Open AccessArticle

Altered Structural Expression and Enzymatic Activity Parameters in Quiescent Ulcerative Colitis: Are These Potential Normalization Criteria?

1
Digestive Disease Center, Bispebjerg Hospital, 2400 Copenhagen, Denmark
2
Wellcome Centre for Cell-Matrix Research, Division of Cell Matrix and Regenerative Medicine, Faculty of Biology Medicine and Health, University of Manchester, Manchester M16 8FB, UK
3
Department of Pathology, Herlev Hospital, 2730 Copenhagen, Denmark
4
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
5
Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
6
Institute of Clinical Physiology/Nutritional Medicine, Department of Gastroenterology, Rheumatology and Infectious Diseases, Charité—Universitätsmedizin Berlin, 12203 Berlin, Germany
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(5), 1887; https://doi.org/10.3390/ijms21051887
Received: 10 February 2020 / Revised: 3 March 2020 / Accepted: 5 March 2020 / Published: 10 March 2020
(This article belongs to the Special Issue Update on Basic and Molecular Research in Inflammatory Bowel Disease)
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. View Full-Text
Keywords: Inflammatory bowel disease; ulcerative colitis; mucosal healing; mucosal barrier integrity; tight junction; short-circuit current; PGE2; COX-1; COX-2 Inflammatory bowel disease; ulcerative colitis; mucosal healing; mucosal barrier integrity; tight junction; short-circuit current; PGE2; COX-1; COX-2
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Kjærgaard, S.; Damm, M.M.B.; Chang, J.; Riis, L.B.; Rasmussen, H.B.; Hytting-Andreasen, R.; Krug, S.M.; Schulzke, J.-D.; Bindslev, N.; Hansen, M.B. Altered Structural Expression and Enzymatic Activity Parameters in Quiescent Ulcerative Colitis: Are These Potential Normalization Criteria? Int. J. Mol. Sci. 2020, 21, 1887.

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