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Pathological Study on Epithelial-Mesenchymal Transition in Silicotic Lung Lesions in Rat.
Komai, Mao; Mihira, Karin; Shimada, Akinori; Miyamoto, Ikumi; Ogihara, Kikumi; Naya, Yuko; Morita, Takehito; Inoue, Kenichiro; Takano, Hirohisa.
Afiliación
  • Komai M; Laboratory of Pathology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Sagamihara-shi, Kanagawa 252-5201, Japan.
  • Mihira K; Laboratory of Pathology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Sagamihara-shi, Kanagawa 252-5201, Japan.
  • Shimada A; Laboratory of Pathology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Sagamihara-shi, Kanagawa 252-5201, Japan. a-shimada@azabu-u.ac.jp.
  • Miyamoto I; Laboratory of Pathology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Sagamihara-shi, Kanagawa 252-5201, Japan.
  • Ogihara K; Laboratory of Pathology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Sagamihara-shi, Kanagawa 252-5201, Japan.
  • Naya Y; Laboratory of Pathology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Sagamihara-shi, Kanagawa 252-5201, Japan.
  • Morita T; Department of Veterinary Pathology, Tottori University, 4-101 Koyama Minami, Tottori-shi, Tottori 680-8553, Japan.
  • Inoue K; School of Nursing, University of Shizuoka, Shizuoka-shi, Shizuoka 422-8526, Japan.
  • Takano H; Department of Environmental Engineering, Kyoto University Graduate School of Engineering, Kyoto-shi, Kyoto 615-8530, Japan.
Vet Sci ; 6(3)2019 Aug 30.
Article en En | MEDLINE | ID: mdl-31480326
Silicosis, caused by the inhalation of crystalline silicon dioxide or silica, is one of the most severe occupational diseases. Persistent inflammation and progressive massive pulmonary fibrosis are the most common histological changes caused by silicosis. Association of epithelial-mesenchymal transition (EMT) of hyperplastic type II epithelial cells with the fibrotic events of pulmonary fibrosis has been suggested in in vitro silica-exposed cultured cell models, patients with idiopathic pulmonary fibrosis, and bleomycin-induced experimental models. Histological features of EMT, however, are not fully described in silicotic lungs in in vivo. The purpose of this study was to demonstrate EMT of hyperplastic type II epithelial cells in the developmental process of progressive massive pulmonary fibrosis in the lungs of rats exposed to silica. F344 female rats were intratracheally instilled with 20 mg of crystalline silica (Min-U-Sil-5), followed by sacrifice at 1, 3, 6, and 12 months after instillation. Fibrosis, characterized by the formation of silicotic nodules, progressive massive fibrosis, and diffuse interstitial fibrosis, was observed in the lungs of the treated rats; the effects of fibrosis intensified in a time-dependent manner. Hyperplasia of the type II epithelial cells, observed in the massive fibrotic lesions, dominated in the lungs of rats at 6 and 12 months after the treatment. Immunohistochemistry of the serial sections of the lung tissues demonstrated positive labeling for cytokeratin, vimentin, and α-smooth muscle actin in spindle cells close to the foci of hyperplasia of type II epithelial cells. Spindle cells, which exhibited features of both epithelial cells and fibroblasts, were also demonstrated with bundles of collagen fibers in the fibrotic lesions, using electron microscopy. Increased expression of TGF-ß was shown by Western blotting and immunohistochemistry in the lungs of the treated rats. These findings suggested that enhanced TGF-ß expression and EMT of hyperplastic type II epithelial cells are involved in the development process of progressive massive pulmonary fibrosis during silicosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Vet Sci Año: 2019 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Vet Sci Año: 2019 Tipo del documento: Article País de afiliación: Japón
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