title: Effects of Chrysotile Exposure in Human Bronchial Epithelial Cells: Insights into the Pathogenic Mechanisms of Asbestos-Related Diseases.
abstract: Chrysotile asbestos accounts for > 90% of the asbestos used worldwide, and exposure is associated with asbestosis (asbestos-related fibrosis) and other malignancies; however, the molecular mechanisms involved are not fully understood. A common pathogenic mechanism for these malignancies is represented by epithelial-mesenchymal transition (EMT), through which epithelial cells undergo a morphological transformation to assume a mesenchymal phenotype. In the present work, we propose that chrysotile asbestos induces EMT through a mechanism involving a signaling pathway mediated by tranforming growth factor beta (TGF-β).
  
  
  
  We investigated the role of chrysotile asbestos in inducing EMT in order to elucidate the molecular mechanisms involved in this event.
  
  
  
  Human bronchial epithelial cells (BEAS-2B) were incubated with 1 μg/cm2 chrysotile asbestos for ≤ 72 hr, and several markers of EMT were investigated. Experiments with specific inhibitors for TGF-β, glycogen synthase kinase-3β (GSK-3β), and Akt were performed to confirm their involvement in asbestos-induced EMT. Real-time polymerase chain reaction (PCR), Western blotting, and gelatin zymography were performed to detect mRNA and protein level changes for these markers.
  
  
  
  Chrysotile asbestos activated a TGF-β-mediated signaling pathway, implicating the contributions of Akt, GSK-3β, and SNAIL-1. The activation of this pathway in BEAS-2B cells was associated with a decrease in epithelial markers (E-cadherin and β-catenin) and an increase in mesenchymal markers (α-smooth muscle actin, vimentin, metalloproteinases, and fibronectin).
  
  
  
  Our findings suggest that chrysotile asbestos induces EMT, a common event in asbestos-related diseases, at least in part by eliciting the TGF-β-mediated Akt/GSK-3β/SNAIL-1 pathway.
  
  
  
  Gulino GR, Polimeni M, Prato M, Gazzano E, Kopecka J, Colombatto S, Ghigo D, Aldieri E. 2016. Effects of chrysotile exposure in human bronchial epithelial cells: insights into the pathogenic mechanisms of asbestos-related diseases. Environ Health Perspect 124:776-784; http://dx.doi.org/10.1289/ehp.1409627.
authors.affiliation: Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates "G. Scansetti," University of Torino, Torino, Italy.
authors.forename: Giulia Rossana
authors.initials: GR
authors.lastname: Gulino
authors.forename: Manuela
authors.initials: M
authors.lastname: Polimeni
authors.forename: Mauro
authors.initials: M
authors.lastname: Prato
authors.forename: Elena
authors.initials: E
authors.lastname: Gazzano
authors.forename: Joanna
authors.initials: J
authors.lastname: Kopecka
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Colombatto
authors.forename: Dario
authors.initials: D
authors.lastname: Ghigo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Aldieri
mesh_terms: D017632:Asbestos, Serpentine / Q000633:toxicity*; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D000071250:Snail Family Transcription Factors / Q000378:metabolism
chemical_list: D017632:Asbestos, Serpentine; D000071250:Snail Family Transcription Factors; D000071679:Glycogen Synthase Kinase 3 beta