期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 113, 期 7, 页码 2234-2247出版社
WILEY
DOI: 10.1002/jcb.24094
关键词
EMT; ASBESTOS EXPOSURE ASSOCIATED DISEASES; FIBROSIS; CANCER
资金
- Academy of Finland
- Finnish Cancer Foundation
- Sigrid Juselius Foundation
- Yrjo Jahnsson Foundation
- Magnus Ehrnrooth Foundation
- Biocentrum Helsinki
- Helsinki University
- University of Helsinki
- Jalmari and Rauha Ahokas Foundation
- Foundation of the Finnish Anti-Tuberculosis Association
- Finnish Cultural Foundation
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 cellcell contacts, actin reorganization and expression of a-smooth muscle actin (a-SMA) in 2D cultures. These phenotypic changes were not associated with increased transforming growth factor (TGF)-beta 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: 22342247, 2012. (c) 2012 Wiley Periodicals, Inc.
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