ABSTRACT
BACKGROUND: The transforming growth factor ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/ß-catenin pathway plays an important role, notably with regard to TGF-ß1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-ß1-induced EMT, although the underlying mechanism have not yet been fully elucidated. METHODS: Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-ß1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and ß-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/ß-catenin signaling pathway was analyzed using the Top/Fop flash reporters. RESULTS: Both 1α, 25(OH)2D3 and ICG-001 blocked TGF-ß1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)2D3 suppressed the activity of the Wnt/ß-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001. CONCLUSION: 1α, 25(OH)2D3 synergizes with ICG-001 and inhibits TGF-ß1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/ß-catenin signaling pathway.