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