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
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.