(c) 2016 Jon L Gelman, All Rights Reserved.

Wednesday, December 23, 2015

Chrysotile asbestos induces EMT, a common event in asbestos-related diseases

Background: Chrysotile asbestos accounts for more than 90% of the asbestos used worldwide and exposure is associated with asbestosis (asbestos-related fibrosis) and other malignancies, but 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 take on a mesenchymal phenotype. In the present work we propose that chrysotile asbestos induces EMT through a mechanism involving a Tranforming Growth Factor beta (TGFβ)-mediated signaling pathway.

Objectives: To investigate the role of chrysotile asbestos in inducing EMT trying to elucidate the molecular mechanisms involved in this event.

Methods: Human bronchial epithelial cells BEAS-2B were incubated with 1 µg/cm2 chrysotile asbestos for up to 72 h and several markers of EMT were investigated. Experiments with the specific inhibitors for TGF-β, Glycogen Synthase Kinase-3β (GSK-3β) and Akt were carried out in order to confirm their involvement in asbestos-induced EMT. Real time PCR, Western blot and gelatin zymographies were performed to detect the mRNA and protein expression changes of these markers.

Results: Chrysotile asbestos activates a TGF-β-mediated signaling pathway, which implicates the contribution of Akt, GSK-3β, and SNAIL-1. The activation of this pathway in BEAS-2B cells was associated with a decrease in the epithelial markers (E-cadherin and β-catenin), and an increase in the mesenchymal markers (α-smooth muscle actin, vimentin, metalloproteinases and fibronectin).

Conclusions: 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.

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Jon L. Gelman of Wayne NJ is the author of NJ Workers’ Compensation Law (West-Thompson-Reuters) and co-author of the national treatise, Modern Workers’ Compensation Law (West-Thompson-Reuters). For over 4 decades the Law Offices of Jon L Gelman  1.973.696.7900  have been representing injured workers and their families who have suffered occupational accidents and illnesses.