dc.contributor.author
Awad, Karem
dc.contributor.author
Barmeyer, Christian
dc.contributor.author
Bojarski, Christian
dc.contributor.author
Nagel, Oliver
dc.contributor.author
Lee, In-Fah M.
dc.contributor.author
Schweiger, Michal R.
dc.contributor.author
Schulzke, Jörg-Dieter
dc.contributor.author
Bücker, Roland
dc.date.accessioned
2023-09-08T15:35:16Z
dc.date.available
2023-09-08T15:35:16Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/40783
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-40504
dc.description.abstract
Background: The underlying pathophysiology of irritable bowel syndrome (IBS) is still unclear. Our aim was to investigate the pathophysiological mechanisms of diarrhea, constipation, and antigen uptake in mixed-type IBS (IBS-M).
Methods: Colonoscopic biopsies were obtained from IBS-M patients. Epithelial transport and barrier function of colonic mucosae were characterized in Ussing chambers using impedance spectroscopy. Mucosal permeability to macromolecules was measured. Western blotting for tight junction (TJ) proteins was performed and their subcellular localization was visualized by confocal microscopy. RNA-sequencing was performed for gene expression and signaling pathway analysis.
Results: In IBS-M, epithelial resistance and ENaC-dependent sodium absorption were unchanged, while short-circuit current reflecting chloride secretion was reduced. Concomitantly, epithelial permeability for fluorescein and FITC-dextran-4000 increased. TJ protein expression of occludin decreased, whereas claudins were unaltered. Confocal microscopy revealed the de-localization of tricellulin from tricellular TJs. Involved pathways were detected as proinflammatory cytokine pathways, LPS, PGE2, NGF, and vitamin D.
Conclusions: Decreased anion secretion explains constipation in IBS-M, while ion permeability and sodium absorption were unaltered. Reduced occludin expression resulted in the delocalization of tricellulin from the tricellular TJ, leading to increased macromolecular permeability that contributes to antigen influx into the mucosa and perpetuates a low-grade inflammatory process.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
irritable bowel syndrome
en
dc.subject
intestinal barrier function
en
dc.subject
tight junctions
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Impaired Intestinal Permeability of Tricellular Tight Junctions in Patients with Irritable Bowel Syndrome with Mixed Bowel Habits (IBS-M)
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
236
dcterms.bibliographicCitation.doi
10.3390/cells12020236
dcterms.bibliographicCitation.journaltitle
Cells
dcterms.bibliographicCitation.number
2
dcterms.bibliographicCitation.originalpublishername
MDPI
dcterms.bibliographicCitation.volume
12
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
36672170
dcterms.isPartOf.eissn
2073-4409