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Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease
Citation
Sohal, SS and Reid, D and Soltani, A and Ward, C and Weston, S and Muller, HK and Wood-Baker, R and Walters, EH, Reticular basement membrane fragmentation and potential epithelial mesenchymal transition is exaggerated in the airways of smokers with chronic obstructive pulmonary disease , Respirology, 15, (6) pp. 930-938. ISSN 1323-7799 (2010) [Refereed Article]
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The definitive published version is available online at: http://interscience.wiley.com
DOI: doi:10.1111/j.1440-1843.2010.01808.x
Abstract
Background and objective: In COPD, the airways are
chronically inflamed, and we have now observed fragmentation
of the reticular basement membrane
(Rbm). This appears to be a hallmark of the process
known as epithelial mesenchymal transition (EMT), in
which epithelial cells migrate through the Rbm and
differentiate into fibroblasts. The aim of this study was
to confirm the extent and relevance of Rbm fragmentation
in smokers and patients with COPD, and to
undertake a preliminary analysis of some classical
markers of EMT.
Methods: Endobronchial biopsies from current
smokers (CS; n = 17) and ex-smokers with COPD
(ES; n = 15), smokers with normal lung function (NS;
n = 16) and never-smoking control subjects (NC;
n = 15) were stained for the EMT markers, S100A4,
vimentin, epidermal growth factor receptor and matrix
metalloproteinase-9.
Results: Compared with NC, there was significant
Rbm fragmentation in the CS, ES and NS groups, which
was positively associated with smoking history in subjects
with COPD. Staining for basal epithelial S100A4,
epithelial epidermal growth factor receptor and matrix
metalloproteinase-9 in cells within Rbm clefts, and for
S100A4 inRbmcells,was increased in the CS,NS and ES
groups compared with the NC group. There was also
increased Rbm cell S100A4 staining in the CS group
compared with the ES and NS groups. Basal epithelial
cell staining for S100A4 was inversely correlated with
airflow limitation. Double staining for both S100A4
and vimentin further strengthened the likelihood that
these changes represented active EMT.
Conclusions: This is the first detailed description of
fragmentation and cellularity of the Rbm in smokers,
which were most marked in subjects with COPD. The
data are consistent with active EMT in these subjects.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | cleft, epithelial mesenchymal transition, matrix metalloproteinase-9, S100A4, vimentin |
| 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, D (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: | 64862 |
| Year Published: | 2010 |
| Web of Science® Times Cited: | 77 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2010-09-08 |
| Last Modified: | 2012-01-20 |
| Downloads: | 0 |
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