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Role of epithelial-mesenchymal transition (EMT) and fibroblast function in cerium oxide nanoparticles-induced lung fibrosis
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Mar 16 2017
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Source: Toxicol Appl Pharmacol. 323:16-25
[PDF-1.71 MB]
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Alternative Title:Toxicol Appl Pharmacol
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Description:The emission of cerium oxide nanoparticles (CeO|) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO| induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO|-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO| (0.15 to 7mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure. The results show that at 28days after CeO| (3.5mg/kg) exposure, lung fibrosis was evidenced by increased soluble collagen in bronchoalveolar lavage fluid, elevated hydroxyproline content in lung tissues, and enhanced sirius red staining for collagen in the lung tissue. Lung fibroblasts and alveolar type II (ATII) cells isolated from CeO|-exposed rats at 28days post-exposure demonstrated decreasing proliferation rate when compare to the controls. CeO| exposure was cytotoxic and altered cell function as demonstrated by fibroblast apoptosis and aggregation, and ATII cell hypertrophy and hyperplasia with increased surfactant. The presence of stress fibers, expressed as α-smooth muscle actin (SMA), in CeO|-exposed fibroblasts and ATII cells was significantly increased compared to the control. Immunohistofluorescence analysis demonstrated co-localization of TGF-β or α-SMA with prosurfactant protein C (SPC)-stained ATII cells. These results demonstrate that CeO| exposure affects fibroblast function and induces EMT in ATII cells that play a role in lung fibrosis. These findings suggest potential adverse health effects in response to CeO| nanoparticle exposure.
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Pubmed ID:28315692
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Pubmed Central ID:PMC6341478
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Volume:323
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