Epithelial-Mesenchymal Transition in Chronic Hypersensitivity Pneumonitis

• Published in: Journal of Medical and Dental Sciences Vol. 59; no. 1; pp. 29 - 41
• Main Authors: Yasui, Makito, Miyazaki, Yasunari, Mitaka, Keiko, Ishizuka, Masahiro, Unoura, Koji, Tamaoka, Meiyo, Sumi, Yuki, Inase, Naohiko
• Format: Journal Article
• Language: English
• Published: Japan Tokyo Medical and Dental University 2012
• Subjects: Actins - analysis; Animals; Bronchioles - pathology; Cadherins - analysis; Collagen - analysis; Disease Models, Animal; DNA-Binding Proteins - analysis; Epithelial Cells - pathology; Epithelial-Mesenchymal Transition - physiology; Fibroblasts - pathology; Humans; Interleukin-13 - analysis; Interleukin-4 - analysis; Lung Diseases, Interstitial - pathology; Macrophages - pathology; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Myofibroblasts - pathology; Myofibroblasts - physiology; Pulmonary Alveoli - pathology; Pulmonary Fibrosis - classification; Pulmonary Fibrosis - pathology; Th1 Cells - pathology; Th2 Cells - pathology; Transcription Factors; Transforming Growth Factor beta1 - analysis
• ISSN: 1342-8810; 2185-9132
• DOI: 10.11480/jmds.590104

Chronic hypersensitivity pneumonitis (HP) causes progressive and irreversible pulmonary fibrosis, a disease also observed in conjunction with idiopathic pulmonary fibrosis (IPF). Previous studies have demonstrated that the myofibroblast, a cell type whose origins involve the epithelial-mesenchymal transition (EMT), may play a role in the pathogenesis of IPF. The goal of this study was to determine whether EMT has a role in the pathogenesis of chronic HP. Lung specimens from a chronic HP model and from patients with chronic HP were analyzed. Cellular co-localization of epithelial and mesenchymal markers on the same alveolar epithelial cells (AECs) were examined using immunohistochemistry and cadherin switching by western blotting as indicators of EMT. EMT cells in the AECs were significantly more prevalent in lung specimens from Th2-prone A/J mice than in specimens from Th1-prone C57BL/6 mice. The percentage of EMT cells was correlated with the mRNA expressions of IL-13 and TGF-/β1, the fibrosis score, and the collagen content in the A/J mice. In human, EMT cells in the AECs were significantly more prevalent in lungs specimens from patients with usual interstitial pneumonia pattern than in specimens from patients with nonspecific interstitial pneumonia pattern at the moderate stage of fibrosis. In conclusion, EMT may play an important role in the fibrotic process of chronic HP under the Th2-biased environment.