Renal disease is a major global public health issue that affects 10% of the general population with premature morbidity and mortality related to cardiovascular disease and infection. Interstitial fibrosis is a common hallmark of progressive kidney dysfunction. There remains a stubborn discrepancy in identifying which patients suffer adverse events because of their disease or resulting treatment. Investigation in patient genome variation may explain this discrepancy. Caveolin-1 is the essential structural protein for caveolae that are ubiquitously distributed in fibroblasts, endothelial and epithelial cells. They act as molecular chaperones for transcellular signaling such as degradation of the activated TGFβ-1 receptor. In this thesis, caveolin-1 single nucleotide polymorphism rs4730751 CC genotype is shown to be associated with a better outcome in renal patients for arterial stiffness, and reduced mortality from cardiovascular disease, infection, malignancy in ANCA associated vasculitis. By inducing renal models of fibrosis in caveolin-1 knockout mice, deletion of caveolin-1 leads to increased fibrosis. In conclusion, this polymorphism could be used as a marker of disease risk either in isolation or as part of a clinical risk score to counsel patients on the likely prognosis of their condition. Manipulation of caveolin-1 expression may be a therapeutic strategy in reducing renal fibrosis.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:731816 |
| Date | January 2017 |
| Creators | Chand, Sourabh |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/7824/ |
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