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Title: The impact of cigarette smoke on cell survival and inflammation in rat lungs : the role of oxidative stress and VEGF/KDR signalling and its implications in COPD
Author: Marwick, John Alexander
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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A decrease in both VEGF and KDR was observed in rat lungs exposed to cigarette smoke as well as disruption to the other components of their signalling complex, neurophilin-1 and glycpican-1. Impaired survival signalling in rat lungs exposed to cigarette smoke was also demonstrated. These changes were mirrored in both smokers and COPD lungs, indicating that these changes may play a role in cigarette smoke induced COPD. Cigarette smoke-triggered inflammation in COPD may be maintained by a mechanism involving enhanced pro-inflammatory gene transcription. The balance between histone acetylation and deacetylation is a key regulator of the specificity and duration of gene transcription, where an imbalance may result in excessive transcription of specific pro-inflammatory genes in the lungs. Cigarette smoke exposure was shown to result in an influx of inflammatory cells and chromatin remodelling in rat lungs. This was associated with an increase in histone acetylation concomitant with increased mitogen activated protein kinase activation and increased DNA binding of pro-inflammatory transcription factors. Reduced histone deacetylase 2 expression and activity was observed, which may be a result of covalent modification. These findings suggest a plausible molecular mechanism by which cigarette smoke drives pro-inflammatory gene transcription and an inflammatory response in the lungs by oxidative stress activated pathways.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available