title: Epithelial-mesenchymal transition in chronic hypersensitivity pneumonitis.
abstract: 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.
authors.affiliation: Department of Integrated Pulmonology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Makito
authors.initials: M
authors.lastname: Yasui
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Mitaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ishizuka
authors.forename: Koji
authors.initials: K
authors.lastname: Unoura
authors.forename: Meiyo
authors.initials: M
authors.lastname: Tamaoka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sumi
authors.forename: Naohiko
authors.initials: N
authors.lastname: Inase
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D055745:Bronchioles / Q000473:pathology; D015820:Cadherins / Q000032:analysis; D003094:Collagen / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D018793:Interleukin-13 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D017563:Lung Diseases, Interstitial / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D058628:Myofibroblasts / Q000473:pathology / Q000502:physiology; D011650:Pulmonary Alveoli / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000145:classification / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology; D018418:Th2 Cells / Q000473:pathology; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1 / Q000032:analysis
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D015820:Cadherins; D004268:DNA-Binding Proteins; D018793:Interleukin-13; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C504004:Ttf1 protein, mouse; D015847:Interleukin-4; D003094:Collagen