Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial tight junction defects in coeliac disease
| Autor: | C. May, Michael Schumann, Dorothee Günzel, Martine Heyman, Nataly Buergel, Jan F. Richter, Anja Fromm, Joerg-Dieter Schulzke, Michael Fromm, Martin Zeitz, Christian Bojarski, Detlef Sorgenfrei, Hanno Troeger, Severin Daum |
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| Rok vydání: | 2011 |
| Předmět: |
Blotting
Western Cell Apoptosis Cell Cycle Proteins Biology Polymerase Chain Reaction Tight Junctions Protein Phosphatase 1 Cell polarity medicine Humans Biotinylation Intestinal Mucosa Claudin Adaptor Proteins Signal Transducing Microscopy Confocal Tight junction Gastroenterology Cell Polarity Membrane Proteins Signal transducing adaptor protein Phosphoproteins Cell biology Blot Celiac Disease medicine.anatomical_structure Transcytosis Case-Control Studies Paracellular transport Claudins Zonula Occludens-1 Protein |
| Zdroj: | Gut. 61:220-228 |
| ISSN: | 1468-3288 0017-5749 |
| DOI: | 10.1136/gutjnl-2011-300123 |
| Popis: | Background Epithelial barrier defects are well known in coeliac disease, but the mechanisms are only poorly defined. It is unclear, whether barrier disturbance reflects upregulated epithelial transcytosis or paracellular leakage. Objective To characterise the molecular structure and function of the epithelial tight junction (TJ) and mechanisms of its dysregulation. Methods Molecular analysis of proteins involved in TJ assembly and their regulation was performed by western blotting and confocal microscopy correlated to electrophysiology. Results A complex alteration of the composition of epithelial TJ proteins (with more pore-forming claudins like claudin-2 and a reduction in tightening claudins like claudin-3, -5 and -7) was found for protein expression and subcellular localisation, responsible for an increase in paracellular biotin-NHS uptake. In contrast, epithelial apoptosis was only moderately elevated (accounting for a minor portion of barrier defects) and epithelial gross lesions—for example, at cell extrusion zones, were absent. This TJ alteration was linked to an altered localisation/expression of proteins regulating TJ assembly, the polarity complex protein Par-3 and the serine-/threonine phosphatase PP-1. Conclusions Changes in cell polarity proteins Par-3 and PP-1 are associated with altered expression and assembly of TJ proteins claudin-2, -3, -5 and -7 and ZO-1, causing paracellular leakage in active coeliac disease. |
| Databáze: | OpenAIRE |
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