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UBC Theses and Dissertations
Basic mechanism of airway epithelial repair : role of IL-13 and EGFR glycosylation Allahverdian, Sima
Abstract
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.
Item Metadata
Title |
Basic mechanism of airway epithelial repair : role of IL-13 and EGFR glycosylation
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2008
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Description |
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.
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Extent |
4990315 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-03-09
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0067011
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2009-05
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International