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Smoking has potential to initiate epithelial mesenchymal transition (EMT) in the airway mucosa

Citation

Sohal, SS and Reid, DW and Soltani, A and Ward, C and Weston, S and Muller, HK and Wood-Baker, R and Walters, EH, Smoking has potential to initiate epithelial mesenchymal transition (EMT) in the airway mucosa, Respirology, pp. Vol 15 (Suppl. 1), A11-A40. (2010) [Conference Extract]

Abstract

Background Epithelial mesenchymal transition is a process in which airway epithelial cells disaggregate and then migrate through the reticular basement membrane (Rbm) into the lamina propria to become myofibroblasts. The aim of this study was to identify if EMT is active in the airways in smokers, and whether relevant to COPD. Methods Endobronchial biopsies (ebb) from current smokers with COPD (CS; n = 17) and ex-smokers with COPD (ES; n = 15), smokers with normal lung function (NS; n = 16) and never-smoking controls (NC; n = 15) were stained for EMT markers, S100A4 a fibroblast protein, epidermal growth factor receptor (EGFR) and matrix metalloproteinase-9 (MMP-9). Computer-assisted image analysis was used to quantify the expression of markers in biopsies and slides were counted by an observer blinded to subject and diagnosis. We used non-parametric statistics. Results Compared to NC, there was significant fragmentation of the Rbm in CS, ES and NS groups (p < 0.001), which was especially marked in CS and was positively related to pack years in COPD subjects (R = 0.41, p = 0.02). CS, NS and ES demonstrated increased staining for: basal epithelial S100A4 (p < 0.004), epithelial EGFR (p < 0.001) and MMP-9 (p < 0.002) for cells in Rbm ‘clefts’, and Rbm cell S100A4 (p < 0.001) compared to NC. There was increased Rbm cell S100A4 staining in CS vs. ES and NS (p < 0.007). Basal epithelial cells staining for S100A4 correlated negatively with airflow limitation (R = -0.49, p = 0.04) in CS, and dual staining revealed that basal S100A4 positive cells co-stained with vimentin (an additional mesenchymal marker). Conclusions Our findings suggest that EMT is active in smokers, and is most evident in current smokers with COPD, suggesting a role in COPD pathogenesis. Supported by The NHMRC project grant 490023. Conflict of Interest Nil.

Item Details

Item Type:Conference Extract
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Respiratory Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Respiratory System and Diseases (incl. Asthma)
Author:Sohal, SS (Dr Sukhwinder Sohal)
Author:Reid, DW (Dr David Reid)
Author:Soltani, A (Dr Amir Soltani Abhari)
Author:Weston, S (Mr Steven Weston)
Author:Muller, HK (Professor Konrad Muller)
Author:Wood-Baker, R (Professor Richard Wood-Baker)
Author:Walters, EH (Professor Haydn Walters)
ID Code:73030
Year Published:2010
Deposited By:Menzies Institute for Medical Research
Deposited On:2011-09-07
Last Modified:2011-09-14
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