1α, 25-dihydroxyvitamin D3 inhibits transforming growth factor β1-induced epithelial-mesenchymal transition via β-catenin pathway.
10.1097/CM9.0000000000000830
- Author:
Xin-Rong XIONG
1
;
Xin-Li TIAN
2
;
Ru-Jie HUO
3
;
Yan-Ting DONG
3
;
Dai LIU
3
;
Jing-Cui BAI
3
;
Yun-Feng QI
4
;
Xin-Rui TIAN
3
Author Information
1. Shanxi medical university, Taiyuan, Shanxi 030001, China.
2. Cardiopulmonary Center, The Seventh Medical Center of People's Liberation Army General Hospital, Beijing 100730, China.
3. Department of Respiratory and Critical Care Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.
4. Department of Respiratory Medicine, Jinhua Hospital of Traditional Chinese Medicine, Jinhua, Zhejiang 321017, China.
- Publication Type:Journal Article
- From:
Chinese Medical Journal
2020;133(11):1298-1303
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:The transforming growth factor β1 (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 D3(1α, 25(OH)2D3) 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)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-β1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and β-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)2D3 and ICG-001 blocked TGF-β1-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/β-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-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.
