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Title: Sonic hedgehog signalling in chronic renal allograft nephropathy and peripheral immunity
Author: Wakelin, Sonia Jane
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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The first hypothesis central to this thesis was that Shh signalling pathway components are expressed in and relevant to normal and CAN kidney. The results presented demonstrate that, although Shh is expressed in normal renal epithelium, this expression is lost in CAN, a finding in contrast to observations in models of lung fibrosis. Possible reasons for this loss of expression are further investigated using cultures of a renal kidney epithelial cell line (SCHN) and primary cultures of murine epithelial cells. The second hypothesis underlying the work presented in this thesis was that Shh signalling plays a role in peripheral immunity. In particular, the role of Shh signalling in macrophages and effector function of macrophages but that the predominant effects observed are most likely to be due to low levels of endotoxin contamination present within the recombinant proteins utilised to explore the effects of Shh in vitro. Shh also modulated the cytokine effector function but not the proliferation of activated CD4+ T cells, a finding partly in keeping with previous reports in the literature. However, in contrast to previous reports, blockade of Shh signalling failed to abrogate either the proliferation or cytokine effector response of activated CD4+ T cells. Possible reasons for this disparity are discussed. Taken together, the findings from these investigations highlight possible roles for Shh signalling in adult kidney and peripheral immunity but emphasize the need for good quality commercially available reagents to investigate the pathway.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available