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- Title
Epithelial Barrier Dysfunction in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) via Downregulation of Claudin-1.
- Authors
Awad, Karem; Barmeyer, Christian; Bojarski, Christian; Nagel, Oliver; Lee, In-Fah M.; Schweiger, Michal R.; Schulzke, Jörg-Dieter; Bücker, Roland
- Abstract
Background: In patients with diarrhea-predominant irritable bowel syndrome (IBS-D), the diarrheal mechanisms are largely unknown, and they were examined in this study on colon biopsies. Methods: Electrophysiological measurements were used for monitoring functional changes in the diarrheic colon specimens. In parallel, tight junction protein expression was analyzed by Western blot and confocal laser-scanning microscopy, and signaling pathway analysis was performed using RNA sequencing and bioinformatics. Results: Epithelial resistance was decreased, indicating an epithelial leak flux diarrheal mechanism with a molecular correlate of decreased claudin-1 expression, while induction of active anion secretion and impairment of active sodium absorption via the epithelial sodium channel, ENaC, were not detected. The pathway analysis revealed activation of barrier-affecting cytokines TNF-α, IFN-γ, IL-1β and IL-4. Conclusions: Barrier dysfunction as a result of epithelial tight junction changes plays a role in IBS-D as a pathomechanism inducing a leak flux type of diarrhea.
- Subjects
IRRITABLE colon; CLAUDINS; SODIUM channels; TIGHT junctions; DOWNREGULATION; RNA sequencing
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 24, p2846
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12242846