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Asbestos exposure induces alveolar epithelial cell plasticity through MAPK/Erk signaling.
MedLine Citation:
PMID:  22573546     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The inhalation of asbestos fibers is considered to be highly harmful, and lead to fibrotic and/or malignant disease. Epithelial-to-mesenchymal transition (EMT) is a common pathogenic mechanism in asbestos associated fibrotic (asbestosis) and malignant lung diseases. The characterization of molecular pathways contributing to EMT may provide new possibilities for prognostic and therapeutic applications. The role of asbestos as an inducer of EMT has not been previously characterized. We exposed cultured human lung epithelial cells to crocidolite asbestos and analyzed alterations in the expression of epithelial and mesenchymal marker proteins and cell morphology. Asbestos was found to induce downregulation of E-cadherin protein levels in A549 lung carcinoma cells in 2-dimensional (2D) and 3D cultures. Similar findings were made in primary small airway epithelial cells cultured in 3D conditions where the cells retained alveolar type II cell phenotype. A549 cells also exhibited loss of cell-cell contacts, actin reorganization and expression of α-smooth muscle actin (α-SMA) in 2D cultures. These phenotypic changes were not associated with increased transforming growth factor (TGF)-β signaling activity. MAPK/Erk signaling pathway was found to mediate asbestos-induced downregulation of E-cadherin and alterations in cell morphology. Our results suggest that asbestos can induce epithelial plasticity, which can be interfered by blocking the MAPK/Erk kinase activity. J. Cell. Biochem. 113: 2234-2247, 2012. © 2012 Wiley Periodicals, Inc.
Authors:
Jenni A Tamminen; Marjukka Myllärniemi; Marko Hyytiäinen; Jorma Keski-Oja; Katri Koli
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  113     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-05-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2234-47     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Research Programs Unit, Molecular and Cancer Biology and Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland.
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