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Basic mechanism of airway epithelial repair : role of IL-13 and EGFR glycosylation

University of British Columbia

Epithelial regeneration following injury is crucial for restoring epithelial function to its normal state. Epidermal Growth Factor Receptor (EGFR) has an essential role in maintenance and repair of epithelial tissues. Glycosylated structures attached to many glycoproteins including EGFR can modulate protein function. The main goals ofmy doctoral research project have been to investigate: (1) the basic mechanism of airway epithelial repair, focusing on the EGFR and IL-13 pathways and (2) the role of Sialyl Lewis x (sLex) and sLex decoration of EGFR in airway epithelial repair. In chapter II, we showed that injured Airway Epithelial Cells (AEC) release EGFR ligands (EGF and HB EGF) and IL-13 during repair. Moreover, for the first time, we demonstrated that IL-13 plays an important role in epithelial repair, and that its effect is mediated through release of HB-EGF and activation of EGFR. We found that the reparative effects of IL-13 on AEC are mediated via IL-l3Ra2. This receptor was thought to act only as a decoy receptor until recently. In chapter III, we demonstrated an important role for a specific fucose-containing carbohydrate structure, sLex, in bronchial epithelial repair. In chapter IV we showed that sLex decorates EGFR on Primary Normal Human Bronchial Epithelial (NHBE) cells and that EGFR decoration with sLex increases after mechanical injury. Fucosyltransferase IV (FucT-IV) showed to mediate sLex synthesis in AEC and demonstrated a temporal expression during epithelial repair. Using small interfering RNA (siRNA) and blocking antibody for sLex we found that sLex has an important role in modulating EGFR activity during epithelial repair.

Thesis/Dissertation

application/pdf

2009-03-09

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/5735

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/