Next Article in Journal
A Cellular Model of Infection with Brucella melitensis in Ovine Macrophages: Novel Insights for Intracellular Bacterial Detection
Previous Article in Journal
Effects of 3 Different Commercial Vaccines Formulations against BVDV and BHV-1 on the Inflammatory Response of Holstein Heifers
Open AccessArticle

Pathological Study on Epithelial-Mesenchymal Transition in Silicotic Lung Lesions in Rat

1
Laboratory of Pathology, School of Life and Environmental Science, Azabu University, 1-17-71 Fuchinobe, Sagamihara-shi, Kanagawa 252-5201, Japan
2
Department of Veterinary Pathology, Tottori University, 4-101 Koyama Minami, Tottori-shi, Tottori 680-8553, Japan
3
School of Nursing, University of Shizuoka, Shizuoka-shi, Shizuoka 422-8526, Japan
4
Department of Environmental Engineering, Kyoto University Graduate School of Engineering, Kyoto-shi, Kyoto 615-8530, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Vet. Sci. 2019, 6(3), 70; https://doi.org/10.3390/vetsci6030070
Received: 6 August 2019 / Revised: 27 August 2019 / Accepted: 27 August 2019 / Published: 30 August 2019
(This article belongs to the Section Anatomy, Histology and Pathology)
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-β was shown by Western blotting and immunohistochemistry in the lungs of the treated rats. These findings suggested that enhanced TGF-β expression and EMT of hyperplastic type II epithelial cells are involved in the development process of progressive massive pulmonary fibrosis during silicosis. View Full-Text
Keywords: epithelial-mesenchymal transition; fibrosis; rat; silicosis; TGF-β; type II epithelial cells epithelial-mesenchymal transition; fibrosis; rat; silicosis; TGF-β; type II epithelial cells
Show Figures

Figure 1

MDPI and ACS Style

Komai, M.; Mihira, K.; Shimada, A.; Miyamoto, I.; Ogihara, K.; Naya, Y.; Morita, T.; Inoue, K.; Takano, H. Pathological Study on Epithelial-Mesenchymal Transition in Silicotic Lung Lesions in Rat. Vet. Sci. 2019, 6, 70.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop