Pathological Study on Epithelial-Mesenchymal Transition in Silicotic Lung Lesions in Rat
| Autor: | Ken-ichiro Inoue, Akinori Shimada, Mao Komai, Takehito Morita, Hirohisa Takano, Kikumi Ogihara, Yuko Naya, Ikumi Miyamoto, Karin Mihira |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
TGF-β
Pathology medicine.medical_specialty epithelial-mesenchymal transition Article 03 medical and health sciences Idiopathic pulmonary fibrosis Cytokeratin 0302 clinical medicine Fibrosis Silicosis silicosis Pulmonary fibrosis medicine rat Epithelial–mesenchymal transition 030304 developmental biology 0303 health sciences lcsh:Veterinary medicine Lung General Veterinary business.industry Progressive massive fibrosis fibrosis respiratory system medicine.disease medicine.anatomical_structure 030220 oncology & carcinogenesis lcsh:SF600-1100 business type II epithelial cells |
| Zdroj: | Veterinary Sciences Volume 6 Issue 3 Veterinary Sciences, Vol 6, Iss 3, p 70 (2019) |
| ISSN: | 2306-7381 |
| DOI: | 10.3390/vetsci6030070 |
| Popis: | 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 &alpha 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-&beta was shown by Western blotting and immunohistochemistry in the lungs of the treated rats. These findings suggested that enhanced TGF-&beta expression and EMT of hyperplastic type II epithelial cells are involved in the development process of progressive massive pulmonary fibrosis during silicosis. |
| Databáze: | OpenAIRE |
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