Desmoglein 2, but not desmocollin 2, protects intestinal epithelia from injury
| Autor: | Rudolf E. Leube, Gabriel M. Schacht, Christian Preisinger, Nicolas Schlegel, Claudia A. Krusche, Gernot Sellge, Hanna Ungewiss, Peter Boor, Annika Gross, Michael Meir, Pavel Strnad, Christian Trautwein, Lotta Antonia Pauline Pack, Arnd Heuser, Nurdan Guldiken, Sebastian Kant, Jens Waschke |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine Galectin 3 Immunology Desmoglein-2 Cell junction Desmoglein Mice Young Adult 03 medical and health sciences Crohn Disease Cell Adhesion medicine Animals Humans Immunology and Allergy HSP70 Heat-Shock Proteins Intestinal Mucosa Cell adhesion Aged Desmocollins Mice Knockout Desmoglein 2 Membrane Glycoproteins DSC2 Intestinal permeability Tight junction Chemistry Desmosomes Middle Aged medicine.disease Cell biology Mice Inbred C57BL 030104 developmental biology Desmocollin |
| Zdroj: | Mucosal Immunology. 11:1630-1639 |
| ISSN: | 1933-0219 |
| Popis: | Desmosomes are the least understood intercellular junctions in the intestinal epithelia and provide cell-cell adhesion via the cadherins desmoglein (Dsg)2 and desmocollin (Dsc)2. We studied these cadherins in Crohn's disease (CD) patients and in newly generated conditional villin-Cre DSG2 and DSC2 knockout mice (DSG2ΔIEC; DSC2ΔIEC). CD patients exhibited altered desmosomes and reduced Dsg2/Dsc2 levels. The intestines of both transgenic animal lines were histopathologically inconspicuous. However, DSG2ΔIEC, but not DSC2ΔIEC mice displayed an increased intestinal permeability, a wider desmosomal space as well as alterations in desmosomal and tight junction components. After dextran sodium sulfate (DSS) treatment and Citrobacter rodentium exposure, DSG2ΔIEC mice developed a more-pronounced colitis, an enhanced intestinal epithelial barrier disruption, leading to a stronger inflammation and activation of epithelial pSTAT3 signaling. No susceptibility to DSS-induced intestinal injury was noted in DSC2ΔIEC animals. Dsg2 interacted with the cytoprotective chaperone Hsp70. Accordingly, DSG2ΔIEC mice had lower Hsp70 levels in the plasma membrane compartment, whereas DSC2ΔIEC mice displayed a compensatory recruitment of galectin 3, a junction-tightening protein. Our results demonstrate that Dsg2, but not Dsc2 is required for the integrity of the intestinal epithelial barrier in vivo. |
| Databáze: | OpenAIRE |
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