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Evidence of epithelial-mesenchymal transition in COPD?


Sohal, SS and Reid, DW and Ward, C and Weston, S and Wood-Baker, R and Walters, EH, Evidence of epithelial-mesenchymal transition in COPD?, The Thoracic Society of Australia & New Zealand Annual Scientific Meeting, April, Darwin, Australia (2009) [Conference Extract]


Background: One of the features associated with smoking-related chronic obstructive pulmonary disease (COPD) is lung remodelling. There are suggestions that airway epithelial cells may develop a fibroblast like phenotype and migrate into the subepithelial lamina propria to contribute to airway fibrosis through a process termed "epithelial mesenchymal transition" (EMT). The aim of this study was to identify markers of EMT in endobronchial biopsies from COPD subjects. Methods: Endobronchial biopsies from 11 COPD current smokers and 13 normal non-smokers were stained for: epidermal growth factor receptor (EGFR) which mediates cell migration and differentiation; matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme that assists migration through the reticular basement membrane (RBM); and S100A4 a fibroblast protein. 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. Results: Percentage of epithelial staining for EGFR was significantly increased in COPD smokers compared to normal subjects (42.6 (SD 22.2) vs 7.9 (SD 5.2), p<0.001), MMP-9 and S100A4 epithelial staining was not different between the two groups. We found that the RBM in COPD was highly fragmented with many clefts evident. There was a marked increase in MMP-9 staining of cells within the RBM of COPD compared to normal subjects (3.2 (SD 6.5) vs 0.1 (SD 0.2), p=0.001) and also for S100A4, (47.8 (SD 21.6) vs 6.4 (SD 3.8), p<0.001) per mm of RBM. Conclusions: This is the first description of expression of MMP-9 and S100A4 positive cells in the RBM in COPD and suggests that cells are migrating from surface airway layer into the RBM and possibly the lamina propria. Increased expression of EGFR in the epithelium suggests that these cells may be primed for migration and fibroblast differentiation.

Item Details

Item Type:Conference Extract
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Respiratory diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Sohal, SS (Dr Sukhwinder Sohal)
UTAS Author:Reid, DW (Dr David Reid)
UTAS Author:Ward, C (Dr Christopher Ward)
UTAS Author:Weston, S (Mr Steven Weston)
UTAS Author:Wood-Baker, R (Professor Richard Wood-Baker)
UTAS Author:Walters, EH (Professor Haydn Walters)
ID Code:73036
Year Published:2009
Deposited By:Menzies Institute for Medical Research
Deposited On:2011-09-07
Last Modified:2011-09-14

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