Vitamin D (VitD) has an anti-fibrotic effect on fibrotic lungs. It reduces epithelial-mesenchymal transition (EMT) on tumors. We aimed to investigate target proteins of VitD for the regression of EMT-mediated myofibroblast differentiation. A group of A549 cells were treated with 5 % cigarette smoke extract (CSE) and 5 %CSE + TGF-β (5 ng/ml) to induce EMT. The others were treated with 50 nM VitD 30 min before %5CSE and TGF-β treatments. All cells were collected at 24, 48 and 72 h following 5 %CSE and TGF-β administrations. The expression of p120ctn and NEDD9 proteins acted on E-cadherin turnover in addition to activations of TGF-β and Wnt pathways were examined in these cells and fibrotic human lungs. CSE and TGF-β induced EMT by reducing E-cadherin, p-VDR, SMAD7 and DKK1, increasing α-SMA, p120ctn, Kaiso, NEDD9 and stimulating TGF-β and Wnt/β-catenin signalings in A549 cells. VitD administration reversed these alterations and regressed EMT. Co-immunoprecipitation analysis revealed p-VDR interaction with β-catenin and Kaiso in fibrotic and non-fibrotic human lungs. VitD pre-treatments reduced TGF-β and Wnt/β-catenin signalings by increasing p-VDR, protected from E-cadherin degradation and led to the regression of EMT in A549 cells treated with CSE and TGF-β. Finally, VitD supplementation combined with anti-fibrotic therapeutics can be suggested for treatment of pulmonary fibrosis, which may be developed by smoking, in cases of VitD deficiency.

维生素D（VitD）对纤维化肺具有抗纤维化作用。它减少了肿瘤上皮-间质转化（EMT）。我们旨在研究VitD的靶蛋白，用于EMT介导的成肌纤维细胞分化的回归。一组A549细胞用5％香烟烟雾提取物（CSE）和5％CSE +TGF-β（5 ng / ml）处理以诱导EMT。其他人在％5CSE和TGF-β治疗之前30分钟用50 nM VitD治疗。施用5％CSE和TGF-β后24、48和72小时收集所有细胞。在这些细胞和纤维化的人肺中，还检测了p120ctn和NEDD9蛋白的表达除了激活TGF-β和Wnt途径外，还作用于E-钙粘蛋白更新。CSE和TGF-β通过降低E-钙黏着蛋白，p-VDR，SMAD7和DKK1，增加α-SMA，p120ctn，Kaiso，NEDD9和刺激A549细胞中的TGF-β和Wnt /β-catenin信号传导。VitD管理扭转了这些变化，并使EMT下降了。免疫共沉淀分析显示，在纤维化和非纤维化的人肺中，p-VDR与β-catenin和Kaiso相互作用。VitD预处理通过增加p-VDR降低TGF-β和Wnt /β-catenin信号传导，保护其免受E-钙粘蛋白降解，并导致经CSE和TGF-β处理的A549细胞中EMT退化。最后，可以建议补充VitD与抗纤维化疗法相结合，以治疗肺纤维化，在VitD缺乏的情况下，吸烟可能导致肺纤维化。免疫共沉淀分析显示，在纤维化和非纤维化的人肺中，p-VDR与β-catenin和Kaiso相互作用。VitD预处理通过增加p-VDR降低TGF-β和Wnt /β-catenin信号传导，保护其免受E-钙粘蛋白降解，并导致经CSE和TGF-β处理的A549细胞中EMT退化。最后，可以建议补充VitD与抗纤维化疗法相结合，以治疗肺纤维化，在VitD缺乏的情况下，吸烟可能导致肺纤维化。免疫共沉淀分析显示，在纤维化和非纤维化的人肺中，p-VDR与β-catenin和Kaiso相互作用。VitD预处理通过增加p-VDR降低TGF-β和Wnt /β-catenin信号传导，保护其免受E-钙粘蛋白降解，并导致经CSE和TGF-β处理的A549细胞中EMT退化。最后，可以建议补充VitD与抗纤维化疗法相结合，以治疗肺纤维化，在VitD缺乏的情况下，吸烟可能导致肺纤维化。