Abstract
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. TGFβ1induced 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. TGFβ1overexpression 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.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of the lung with unknown aetiology and a median survival time is 2.8 years from diagnosis [1]
Epithelial injury has been implicated as a driving factor for the pathogenesis of idiopathic pulmonary fibrosis (IPF)
Bleomycin had a gradual increase in mesenchymal cell marker and a decrease in E-cadherin expression that correlated with collagen protein deposition
Summary
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of the lung with unknown aetiology and a median survival time is 2.8 years from diagnosis [1]. Treatment of IPF patients with anti-inflammatory drugs has had little desired effect on the disease, suggesting that the pathogenesis of IPF is yet to be fully explained. Alveolar type II cell injury is an early feature in IPF [8], with increased mediators of alveolar cell apoptosis in IPF lung biopsies and bronchoalveolar lavage being observed [9]. Phenotypic changes in epithelial cells have been reported in the lungs of IPF patients, whereby epithelial cells express mesenchymal markers concomitantly [10]. Due to this immunohistochemical phenomenon, it has been
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