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10.1186/s12989-016-0138-4

http://scihub22266oqcxt.onion/10.1186/s12989-016-0138-4
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suck abstract from ncbi


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pmid27251132
      Part+Fibre+Toxicol 2016 ; 13 (1 ): 27
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  • Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-?-mediated Akt/GSK-3?/SNAIL-1 signalling pathway #MMPMID27251132
  • Polimeni M ; Gulino GR ; Gazzano E ; Kopecka J ; Marucco A ; Fenoglio I ; Cesano F ; Campagnolo L ; Magrini A ; Pietroiusti A ; Ghigo D ; Aldieri E
  • Part Fibre Toxicol 2016[Jun]; 13 (1 ): 27 PMID27251132 show ga
  • BACKGROUND: Multi-walled carbon nanotubes (MWCNT) are currently under intense toxicological investigation due to concern on their potential health effects. Current in vitro and in vivo data indicate that MWCNT exposure is strongly associated with lung toxicity (inflammation, fibrosis, granuloma, cancer and airway injury) and their effects might be comparable to asbestos-induced carcinogenesis. Although fibrosis is a multi-origin disease, epithelial-mesenchymal transition (EMT) is recently recognized as an important pathway in cell transformation. It is known that MWCNT exposure induces EMT through the activation of the TGF-?/Smad signalling pathway thus promoting pulmonary fibrosis, but the molecular mechanisms involved are not fully understood. In the present work we propose a new mechanism involving a TGF-?-mediated signalling pathway. METHODS: Human bronchial epithelial cells were incubated with two different MWCNT samples at various concentrations for up to 96 h and several markers of EMT were investigated. Quantitative real time PCR, western blot, immunofluorescent staining and gelatin zymographies were performed to detect the marker protein alterations. ELISA was performed to evaluate TGF-? production. Experiments with neutralizing anti-TGF-? antibody, specific inhibitors of GSK-3? and Akt and siRNA were carried out in order to confirm their involvement in MWCNT-induced EMT. In vivo experiments of pharyngeal aspiration in C57BL/6 mice were also performed. Data were analyzed by a one-way ANOVA with Tukey's post-hoc test. RESULTS: Fully characterized MWCNT (mean length?
  • |Animals [MESH]
  • |Bronchi/*drug effects/metabolism/pathology/ultrastructure [MESH]
  • |Carcinogenicity Tests [MESH]
  • |Cell Line [MESH]
  • |Epithelial-Mesenchymal Transition/*drug effects [MESH]
  • |Glycogen Synthase Kinase 3 beta/metabolism [MESH]
  • |Humans [MESH]
  • |Inhalation Exposure/adverse effects [MESH]
  • |Male [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Microscopy, Electron, Scanning [MESH]
  • |Microscopy, Electron, Transmission [MESH]
  • |Nanotubes, Carbon/chemistry/*toxicity/ultrastructure [MESH]
  • |Particle Size [MESH]
  • |Proto-Oncogene Proteins c-akt/metabolism [MESH]
  • |Pulmonary Fibrosis/chemically induced/metabolism/pathology [MESH]
  • |Respiratory Mucosa/*drug effects/metabolism/pathology/ultrastructure [MESH]
  • |Signal Transduction/*drug effects [MESH]
  • |Snail Family Transcription Factors/metabolism [MESH]
  • |Surface Properties [MESH]


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