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2629183 
Journal Article 
Abstract 
The role of Caveolin-1 in aberrant epithelial repair in response to house dust mite 
Heijink, IH; van Oosterhout, A; Kapus, A; Postma, DS 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A1437 
English 
WOS:000208771000438 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale: There is increasing evidence that impaired epithelial barrier function is involved in airway remodeling in asthma. Disruption of E-cadherin-mediated cell-cell contacts and delocalization of E-cadherin from epithelial junctions has been observed in asthmatic airways. Junctional loss of E-cadherin is a hallmark of epithelial-to-mesenchymal transition (EMT), a key process in tissue remodeling. We have reported that TGF-β increases the vulnerability of airway epithelial cells upon house dust mite (HDM) exposure and that HDM promotes features of EMT in bronchial epithelium when primed with TGF-β.

Aim: The molecular basis for the increased vulnerability and loss of integrity of asthma epithelium, e.g. to proteolytically active allergens including HDM, is currently unknown. Caveolin-1, the main component of caveolae, is known to stabilize junctional expression of E-cadherin/β-catenin. We hypothesize that expression of caveolin-1 is involved in aberrant epithelial repair and/or EMT instead of normal re-epithelialization upon tissue injury.

Methods: We used the human bronchial epithelial cell line 16HBE and we studied barrier function, localization of E-cadherin, caveolin-1 expression and the presence of caveolae-like structures by electron microscopy, in presence/absence of HDM and/or TGF-β. Additionally, we investigated the effects of disruption of caveolae (cyclodextrin, caveolin-1-targeted siRNA) on epithelial barrier function and epithelial activity.

Results: Combination of TGF-β and HDM induced disruption of E-cadherin-mediated cell-cell contacts in 16HBE, in conjunction with downregulation of caveolin-1. Electron microscopy revealed that this was associated with a reduced number of caveolae-like structures. To study whether downregulation of membrane caveolin-1 is important for HDM-induced defects in cell-cell contacts, we disrupted caveolae by cyclodextrin and/or caveolin-1-targeted siRNA. This resulted in decreased E-cadherin expression and moreover, it enhanced the HDM-induced defects in barrier function and E-cadherin expression. Additionally, it induced a migratory/activated epithelial phenotype with respect to phospho-ERK, phospho-EGFR and IL-8 production.

Conclusion: These data suggest that the expression of caveolin-1 may play a crucial role in the maintenance and/or restoration of epithelial barrier function upon HDM-induced injury in presence of TGF-β. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010