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• W1525528026 abstract "A key feature of inflammatory bowel disease (IBD) is disruption of the intestinal epithelial barrier by unknown mechanisms. Integrity of the epithelial barrier is determined by an apical junctional complex that is composed of tight junction (TJ) and adherens junction (AJ). Previous observations have suggested that alterations in the apical junctional complex occur in IBD. Localization studies in mucosal biopsies from IBD patients have revealed disappearance of key TJ (occludin, JAM1, ZO1, claudin 1) and AJ (E-cadherin, β-catenin) proteins from intercellular junctions.In vitro experiments examining the effects of inflammatory cytokines on model intestinal epithelial monolayers suggest that disruption of the epithelial barrier is associated with internalization of transmembrane TJ proteins, JAM1, occludin and claudins 1/4. The mechanism(s) of internalization of intercellular junctions can be modelled in vitro by calcium depletion of confluent epithelial cell monolayers. Using this model, we have observed rapid, orchestrated endocytosis of all AJ and TJ proteins into a subapical cytoplasmic compartment that is independent of caveolae/lipid rafts and macropinocytosis. However, inhibitors of clathrin-mediated endocytosis effectively block internalization of AJs and TJs, and junctional proteins colocalize with clathrin. Interestingly, internalized AJ and TJ proteins enter early endosomes followed by movement to organelles that do not label with markers of late and recycling endosomes, lysosomes or Golgi but appear to represent a unique storage compartment that colocalizes with t-SNARE protein, syntaxin 4. A better understanding of the mechanisms of junctional internalization and recycling will likely provide new insights into the mechanisms of altered barrier function in IBD." @default.
• W1525528026 created "2016-06-24" @default.
• W1525528026 creator A5042841599 @default.
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• W1525528026 date "2004-11-12" @default.
• W1525528026 modified "2023-10-09" @default.
• W1525528026 title "The Epithelium in Inflammatory Bowel Disease: Potential Role of Endocytosis of Junctional Proteins in Barrier Disruption" @default.
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• W1525528026 doi "https://doi.org/10.1002/0470090480.ch9" @default.
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