Effect of Chrysotile Exposure in XXXX Bronchial Epithelial Cells: Insights on the Pathogenic Mechanisms of Asbestos-Related Diseases.

@entity1 @entity82 @entity4245 @entity66 @entity5 @entity5962 @entity3546 @entity2533 @entity2277 @entity9459 @entity1355
BACKGROUND: Chrysotile @entity1355 accounts for more than 90% of the @entity1355 used worldwide and exposure is associated with @entity1355 ( @entity1355 -related @entity82 ) and other @entity5 , but the molecular mechanisms involved are not fully understood. A common pathogenic mechanism for these @entity5 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 @entity1355 induces EMT through a mechanism involving a Tranforming Growth Factor beta ( @entity2533 )-mediated signaling pathway. OBJECTIVES: To investigate the role of chrysotile @entity1355 in inducing EMT trying to elucidate the molecular mechanisms involved in this event. METHODS: @entity1 bronchial epithelial cells BEAS-2B were incubated with 1   g/cm(2) chrysotile @entity1355 for up to 72 h and several markers of EMT were investigated. Experiments with the specific inhibitors for @entity2533 , @entity9459 ( @entity9459 ) and Akt were carried out in order to confirm their involvement in @entity1355 -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 @entity1355 activates a @entity2533 -mediated signaling pathway, which implicates the contribution of Akt, @entity9459 , and @entity4245 . The activation of this pathway in BEAS-2B cells was associated with a decrease in the epithelial markers ( @entity5962 and @entity3546 ), and an increase in the mesenchymal markers (a-smooth muscle actin, @entity2277 , metalloproteinases and fibronectin). CONCLUSIONS: Our findings suggest that chrysotile @entity1355 induces EMT, a common event in @entity66 , at least in part by eliciting the @entity2533 -mediated Akt/ @entity9459 / @entity4245 pathway.
