Table of Contents
ISRN Pulmonology
Volume 2012, Article ID 153971, 11 pages
Research Article

An Assessment of Epithelial and Mesenchymal Phenotypes in Experimental and Clinical Pulmonary Fibrosis

1Department of Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Granta Park, Cambridge CB21 6GH, UK
2Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
3Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, TAC 441S, New Haven, CT 06520, USA
4James Hogg iCAPTURE Centre, Institute for Heart and Lung Health, Vancouver, BC, Canada V6Z 1Y6
5Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada V6Z 1Y6
6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109, USA

Received 11 June 2012; Accepted 12 July 2012

Academic Editors: J. Ho and A. Miyazato

Copyright © 2012 Rebecca Dunmore et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Epithelial injury has been implicated as a driving factor for the pathogenesis of idiopathic pulmonary fibrosis (IPF). In this study we investigated changes in epithelial and mesenchymal markers in experimental models of fibrosis and associated this with IPF. TGFβ1 induced an epithelial to mesenchymal transition (EMT) phenotype in A549 cells and normal human bronchial epithelial cells, with A549 cells exhibiting a more profound transition to a mesenchymal phenotype. TGFβ1 overexpression in the lungs of mice resulted in an early increase in mesenchymal cell markers and apoptotic genes that preceded collagen deposition, suggesting an early epithelial injury triggers the downstream fibrotic response. In contrast, bleomycin had a gradual increase in mesenchymal cell marker and a decrease in E-cadherin expression that correlated with collagen protein deposition. Finally, we compared normal healthy lung tissue with surgical lung biopsies from IPF patients and observed alterations in epithelial and mesenchymal cell markers, as well as an increase in the apoptotic marker GSK3β. Interestingly, the mesenchymal changes were more profound in rapidly progressive patients in comparison to IPF patients with slowing progressing disease. In summary, this study provides evidence of alterations in epithelial and mesenchymal markers in experimental models of lung fibrosis and how these findings are relevant to clinical disease.