title: Dual-immunohistochemistry provides little evidence for epithelial-mesenchymal transition in pulmonary fibrosis.
abstract: Epithelial-mesenchymal transition (EMT) has been considered to be involved in organ fibrogenesis. However, there is few direct evidence of this process in the pathophysiology of pulmonary fibrosis in vivo. Therefore, we tried to verify the involvement of this process in the development of pulmonary fibrosis. Since the co-expressions of epithelial and mesenchymal markers are thought to be a marker of EMT, we performed dual-immuunohistochemistry to assess the co-expressions of these proteins in lung tissues from bleomycin-induced pulmonary fibrosis in mice, and from patients with idiopathic pulmonary fibrosis, and nonspecific interstitial pneumonia. Double positive cells for epithelial markers including E-cadherin, T1alpha, or aquaporin 5, and a mesenchymal markers alpha-smooth muscle actin or vimentin were not found in bleomycin-induced pulmonary fibrosis in mice. Double positive cells for E-cadherin, ICAM-1, LEA, CD44v9, or SP-A and alpha-smooth muscle actin or vimentin were not found in lung tissues from normal lung parenchyma, idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. These results offer at least two possibilities. One is that EMT does not occur in IPF or bleomycin-induced pulmonary fibrosis in mice. Another is that EMT may occur in pulmonary fibrosis but the time during this transition in which cells express detectable levels of epithelial and mesenchymal markers is too small to be detected by double immunohistochemistry.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Yamada
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kuwano
authors.forename: Takashige
authors.initials: T
authors.lastname: Maeyama
authors.forename: Naoki
authors.initials: N
authors.lastname: Hamada
authors.forename: Michihiro
authors.initials: M
authors.lastname: Yoshimi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Michael
authors.initials: M
authors.lastname: Kasper
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin / Q000633:toxicity; D015820:Cadherins / Q000378:metabolism; D016022:Case-Control Studies; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods*; D017563:Lung Diseases, Interstitial / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D013906:Thoracoscopy; D014746:Vimentin / Q000378:metabolism
chemical_list: D000199:Actins; D015415:Biomarkers; D015820:Cadherins; D018960:Hyaluronan Receptors; D014746:Vimentin; D001761:Bleomycin