title: Epithelial-mesenchymal transition contributes to SWCNT-induced pulmonary fibrosis.
abstract: Previous studies suggest that single-walled carbon nanotube (SWCNT) exposure causes pulmonary fibrosis. We investigated the contribution of epithelial-mesenchymal transition (EMT) during SWCNT-induced pulmonary fibrosis. C57BL6 female mice were intratracheally instilled with SWCNT at 80 μg/mouse for up to 56 days. SWCNT exposure caused pulmonary epithelial and mesenchymal injury, followed by granulomatous and fibrotic changes. Immunofluorescence staining demonstrated the increasing occurrence of epithelial-derived fibroblasts up to 42 days post-exposure. Flow cytometry analysis revealed that 42.60% of N-cadherin (N-cad)-positive fibroblasts were derived from pulmonary epithelial cells, and, in separate experiments, 30.68% of SPC positive cells were stained for N-cad at 42 days. These epithelial-derived fibroblasts were functional in collagen production. With the progression of fibrosis, there were increases in the number of hyperplastic epithelial cells stained positively for TGF-β/p-Smad2 or β-catenin. Therefore, EMT contributes significantly to fibroblast expansion. Aberrant activations of TGF-β/p-Smad2 and β-catenin are postulated to induce EMT during SWCNT-induced pathogenic fibrosis.
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan. chang3@mail.ncku.edu.tw
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Chang
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Tsai
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Shi-Xun
authors.initials: SX
authors.lastname: Dai
mesh_terms: D000818:Animals; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D037742:Nanotubes, Carbon; D037661:Pulmonary Surfactant-Associated Proteins; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D016212:Transforming Growth Factor beta; D051176:beta Catenin; D053505:Matrix Metalloproteinases, Secreted