ß-catenin induces A549 alveolar epithelial cell mesenchymal transition during pulmonary fibrosis.
Mol Med Rep
; 11(4): 2703-10, 2015 Apr.
Article
in En
| MEDLINE
| ID: mdl-25435076
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by expansion of the fibroblast and myofibroblast population and extracellular matrix deposition. Although the pathogenic mechanisms of IPF remain to be fully elucidated, there is emerging evidence that fibroblasts and myofibroblasts may be derived partially from alveolar epithelial cells by epithelialmesenchymal transition (EMT). In the present study, A549 cells were treated with different concentrations of Wnt1 and the results indicated that the mRNA and protein expression levels of vimentin, αsmooth muscle actin (αSMA) and collagen â
gradully increased and those of Ecadherin gradully decreased in a concentrationdependent manner. Furthermore, the A549 cells were transfected with ßcatenin plasmid cells, revealing phenotypic changes in the cells from a pebble to a fusiform shape. The mRNA and protein expression levels of of vimentin, αSMA and collagen â
increased significantly, whereas those of Ecadherin decreased significantly. The present study examined the roles of alveolar epithelial cell injury and profibrogenic cytokine release in EMT and their association with the Wnt/ßcatenin signaling pathway in a mouse model of bleomycininduced pulmonary fibrosis. Bronchoalveolar fluid was obtained 7 days after treatment with bleomycin and the A549 cells were incubated for 48 h. An increase in the expression levels of the mesenchymal markers, αSMA, vimentin and collagen â
, and a concomitant decrease in the expression of the epithelial marker, Ecadherin were observed. This corresponded with an increased expression of ßcatenin. When the A549 cells were infected with a lentivirus expressing ßcatenin shRNA, no significant increase was observed in the expression of the mesenchymal cell markers and the expression of Ecadherin did not decrease. These findings demonstrated that activation of the Wnt signaling pathway was capable of inducing an EMT program in the lung epithelial cells through ßcatenin and that injured alveolar epithelium activated the Wnt/ßcatenin signaling pathway, thereby inducing the expansion of the fibroblast/myofibroblast population through EMT. These results suggested that ßcatenin was involved in the formation of lung fibrosis and may provide a theoretical basis for the treatment of IPF.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Fibrosis
/
Beta Catenin
/
Alveolar Epithelial Cells
/
Epithelial-Mesenchymal Transition
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Med Rep
Year:
2015
Document type:
Article