Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555506
Title: The role of Discoidin Domain Receptor 1 in bronchial epithelial repair
Author: Roberts, Mark E.
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2011
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Abstract:
The factors contributing to epithelial repair are not well understood. Epithelial injury leads to cell loss and exposure of the basement membrane, followed by secretion of provisional matrix (composed of collagens) and migration of epithelial cells to close the wound. The molecular processes involved are not well characterized, although growth factors such as EGF have been implicated. This work shows that the collagen I receptor Discoidin Domain Receptor 1 (DDR1) facilitates epithelial repair. Using a wounding model in BEAS-2B cells, DDRl knockdown inhibits epithelial repair while DDRi overexpression augments epithelial repair. It also shows that DDRi overexpression and knockdown in this cell type increase and reduce levels of pro-MMP-2 respectively. MMP-2 is a known mediator of epithelial repair. Further work undertaken in HBECs in a similar wounding model confirmed the effects of DDRi knockdown on epithelial repair. In this wounding model, MMP-7 was also found to be reduced in the presence of DDRl knockdown. DDRl knockdown also led to reduced proliferation although it had no effect on cell viability. In bronchial epithelial samples obtained by bronchoscopy from patients with asthma, and non-asthma controls, immunohistochemical staining for DDRi showed no evidence of a difference between the two groups. Cells were successfully subcultured from some endobronchial biopsies, and these showed characteristic staining for epithelial cell markers. There was no difference in DDRl protein expression between asthma and non-asthma controls in the small number of epithelial cells successfully subcultured.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.555506  DOI: Not available
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