β-catenin induces A549 alveolar epithelial cell mesenchymal transition during pulmonary fibrosis

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 epithelial‑mesenchymal 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, α‑smooth muscle actin (α‑SMA) and collagen Ⅰ gradully increased and those of E‑cadherin gradully decreased in a concentration‑dependent manner. Furthermore, the A549 cells were transfected with β‑catenin plasmid cells, revealing phenotypic changes in the cells from a pebble to a fusiform shape. The mRNA and protein expression levels of of vimentin, α‑SMA and collagen Ⅰ increased significantly, whereas those of E‑cadherin 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/β‑catenin signaling pathway in a mouse model of bleomycin‑induced 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, α‑SMA, vimentin and collagen Ⅰ, and a concomitant decrease in the expression of the epithelial marker, E‑cadherin were observed. This corresponded with an increased expression of β‑catenin. When the A549 cells were infected with a lentivirus expressing β‑catenin shRNA, no significant increase was observed in the expression of the mesenchymal cell markers and the expression of E‑cadherin 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 β‑catenin and that injured alveolar epithelium activated the Wnt/β‑catenin signaling pathway, thereby inducing the expansion of the fibroblast/myofibroblast population through EMT. These results suggested that β‑catenin was involved in the formation of lung fibrosis and may provide a theoretical basis for the treatment of IPF.