Characterising human lung tissue for biomarkers of EMT-fibrosis and functional steroid receptor components in chronic obstructive pulmonary disease (COPD) patients and control subjects

Patel, HJ 2018, Characterising human lung tissue for biomarkers of EMT-fibrosis and functional steroid receptor components in chronic obstructive pulmonary disease (COPD) patients and control subjects , MPhil thesis, University of Salford.

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Abstract

COPD is a poorly reversible airflow obstruction commonly induced by cigarette smoke. Pathology is linked to a series of inflammatory and fibrotic events in the small airways and lung parenchyma; including fibrosis, emphysema and mucus plugging. This work focuses on the inflammatory and fibrotic aspects of COPD pathology. Processes of fibrotic Epithelial to Mesenchymal Transition (EMT) have been identified in heart and kidney disorders and we wished to evaluate if this is a contributing factor in COPD. Second, patient treatment options are limited. Steroid resistance is the major barrier for effective treatment and this study seeks to evaluate steroid receptor expression patterns in COPD patient and control subjects to better understand mechanisms of resistance. The aim of this study is to evaluate EMT (S100A4) and glucocorticoid receptor (TTC5 & S211) component expression in lung tissue of COPD patients and control subjects using immunohistochemical staining. The result obtained describes that S100A4 (EMT marker) was more highly expressed in active smokers (non-smoker and ex-smoker, versus current, p<0.0001). TTC5 expression was higher in both ex-smokers and current smokers compared to NS (p=0.0022). S211 expression levels were similarly raised in both ex and current smokers compared to NS (p=0.0078). The conclusion is that raised S100A4 expression in active smokers indicates EMT and may play a role in fibrosis in COPD via a partially reversible process. Raised TTC5 and S211 in ex and current smokers indicate irreversible glucocorticoid receptor changes and may implicate a mechanism of steroid resistance in COPD patients, thus prompting further research in this area.

Item Type: Thesis (MPhil)
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Depositing User: HJ Patel
Date Deposited: 05 Apr 2018 09:48
Last Modified: 05 Apr 2018 09:48
URI: http://usir.salford.ac.uk/id/eprint/45191

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