Background::The transforming growth factorβ1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)has been proven associated with the pathogenesis of asthmatic airway remodeling,in which the Wnt/β-catenin pathway ...Background::The transforming growth factorβ1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)has been proven associated with the pathogenesis of asthmatic airway remodeling,in which the Wnt/β-catenin pathway plays an important role,notably with regard to TGF-β1.Recent studies have shown that 1α,25-dihydroxyvitamin D 3(1α,25(OH)2D 3)inhibits TGF-β1-induced EMT,although the underlying mechanism have not yet been fully elucidated.Methods::Alveolar epithelial cells were exposed to 1α,25(OH)2D 3,ICG-001,or a combination of both,followed by stimulation with TGF-β1.The protein expression of E-cadherin,α-smooth muscle actin,fibronectin,andβ-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/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results::Both 1α,25(OH)2D 3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells.In addition,the Top/Fop Flash reporters showed that 1α,25(OH)2D 3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes,including MMP-9 and Snail,in synergy with ICG-001.Conclusion::1α,25(OH)2D 3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.展开更多
基金This work was supported by the Natural Science Foundation of Shanxi Province of China[2013011055-1]Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in China{2016[366]}+1 种基金Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province{[2017]144}Key Research and Development Program(International Scientific and Technological cooperation)of Shanxi Province.
文摘Background::The transforming growth factorβ1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)has been proven associated with the pathogenesis of asthmatic airway remodeling,in which the Wnt/β-catenin pathway plays an important role,notably with regard to TGF-β1.Recent studies have shown that 1α,25-dihydroxyvitamin D 3(1α,25(OH)2D 3)inhibits TGF-β1-induced EMT,although the underlying mechanism have not yet been fully elucidated.Methods::Alveolar epithelial cells were exposed to 1α,25(OH)2D 3,ICG-001,or a combination of both,followed by stimulation with TGF-β1.The protein expression of E-cadherin,α-smooth muscle actin,fibronectin,andβ-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/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results::Both 1α,25(OH)2D 3 and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells.In addition,the Top/Fop Flash reporters showed that 1α,25(OH)2D 3 suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes,including MMP-9 and Snail,in synergy with ICG-001.Conclusion::1α,25(OH)2D 3 synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.
