Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.490948
Title: Fibroblast gene expression in pulmonary fibrosis
Author: Renzoni, Elisabetta Augusta
ISNI:       0000 0001 3514 1629
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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Abstract:
Background: Idiopathic pulmonary fibrosis (IPF) has a median survival since diagnosis of2-3 years. Interstitial lung disease associated with systemic sclerosis (SSc-ILD) is characterised by a better survival than IPF. Lung fibroblasts are the main cell type responsible for the excessive extracellular matrix synthesis in lung fibrosis. The pathogenesis offibrosis in both conditions is largely unknown, and it is unclear to what extent it differs between the two. Hypothesis: The gene expression profile of fibroblasts from IPF and SSc-ILD differs from control lung fibroblasts; significant differences between IPF and SSc-ILD fibroblasts could explain the worse survival ofIPF patients. The study of gene profiles in response to pro-fibrotic cytokines transforming growth factor beta (TGFbeta) and endothelin-l (ET-1), could allow insights into their role in fibrotic lung diseases. Methods: The global gene expression profile oflung fibroblasts isolated from IPF, SSc-ILD and control lungs was assessed by using Affymetrix oligonucleotide microarrays. After an exploratory set performed using U95v2 arrays, a second, larger set was performed using the more extensive U133A2 arrays. Response to TGFbeta was evaluated in three fibroblasts lines from each group (IPF, SSc-ILD and controls) ofthe first set. Response to ET-l was evaluated in control fibroblasts alone. To evaluate the role played by ET-1 signalling, gene profiles offibroblasts treated/untreated with dual endothelin receptor antagonist Bosentan were also evaluated. Results: Significant differences in the gene expression patterns between fibrotic and control fibroblasts were observed, particularly in the second set. The pattern ofgene expression did not differ between IPF and SSc-ILD fibroblasts, although changes compared to controls tended to be more extreme in the IPF group. The response to TGFbeta did not differ between fibrotic fibroblasts and controls. A striking similarity to the ET-l induced gene profile was observed in the profile ofIPF and SSc-ILD fibroblasts. The gene expression patterns ofboth SSc-ILD and IPF fibroblasts became more similar to that ofcontrol fibroblasts after treatment with Bosentan. Conclusions: The gene expression profile ofIPF and SSc-ILD lung fibroblasts differs from that of controls. ET-l signalling appears to playa significant role in the observed changes. Lung fibroblasts appear to participate in both fibrotic conditions through similar pathways ofresponse. Differences between the two conditions are probably due to events leading to fibroblast recruitment and activation, rather than to differences in their response pattern.
Supervisor: Not available Sponsor: Not available
Qualification Name: University of London, 2008 Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.490948  DOI: Not available
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