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We aimed to discern the involvement of the epidermal growth factor receptor (EGFR) in allergen-induced epithelial barrier impairment, as we previously observed that house dust mite (HDM) signals through EGFR.<\/jats:p><jats:p>We investigated the junctional integrity of human bronchial epithelial cells using electric cell-substrate impedance sensing and immunofluorescent staining.<\/jats:p><jats:p>HDM induced a rapid, transient fall in epithelial resistance, concomitant with delocalisation of E-cadherin and zona occludens (ZO)-1, and proteolytic cleavage of the latter. EGFR inhibition by AG1478 reduced the HDM-triggered decrease in epithelial resistance and improved restoration of epithelial junctions. Similarly, AG1478 increased epithelial barrier recovery upon electroporation-induced injury, although it delayed the migration phase of the wound healing response. HDM-promoted redistribution of E-cadherin was mediated<jats:italic>via<\/jats:italic>EGFR-dependent activation of protease-activated receptor (PAR)-2, while the concomitant ZO-1 degradation was PAR-2\/EGFR-independent. Importantly, the fibrogenic cytokine transforming growth factor (TGF)-\u03b2 prolonged HDM-induced EGFR phosphorylation and inhibited ligand-induced EGFR internalisation\/degradation, which resulted in sustained E-cadherin and ZO-1 redistribution.<\/jats:p><jats:p>Thus, allergen-induced, PAR-2\/EGFR-mediated signalling decreases epithelial resistance and promotes junction disassembly. The TGF-\u03b2-enhanced EGFR signalling may be an important contributor to barrier dysfunction and increased epithelial vulnerability in response to HDM.<\/jats:p>","DOI":"10.1183\/09031936.00125809","type":"journal-article","created":{"date-parts":[[2010,3,30]],"date-time":"2010-03-30T03:05:45Z","timestamp":1269918345000},"page":"1016-1026","source":"Crossref","is-referenced-by-count":107,"title":["Epidermal growth factor receptor signalling contributes to house dust mite-induced epithelial barrier dysfunction"],"prefix":"10.1183","volume":"36","author":[{"given":"I.H.","family":"Heijink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"van 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