Renal tubulointerstitial fibrosis is a major predictor of progressive glomerular disease. It occurs as a result of persistent inflammation and is characterised by excessive deposition of extracellular matrix (ECM) proteins, including accumulation of type I collagen, the most abundant protein of the ECM. Type I collagen is encoded by two genes, COL1A1 and COL1A2, that are tightly regulated at a transcriptional level. A key aim of this study was to use the previously identified COL1A2 promoter and enhancer sequences in order to identify novel regulatory cis-acting elements and the relevant transcription factors that regulate collagen transcription in cells derived from healthy or diseased kidneys. Moreover, the effects of hypoxia and transforming growth factor beta (TGFβ), which are both profibrotic stimuli, on collagen transcription were studied. TGFβ is known to activate CDP/cux transcription factors which can suppress gene activation; based on this finding the role of CDP/cux in COL1A2 transcriptional regulation was assessed. In conclusion,the work presented in this thesis provides an insight into the complex control mechanisms that regulate collagen transcription in both physiological and pathological conditions.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:513546 |
| Date | January 2009 |
| Creators | Fragiadaki, Maria |
| Contributors | Bou-Gharios, George |
| Publisher | Imperial College London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/10044/1/5533 |
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