1α,25-dihydroxyvitamin D3 Attenuates TGF-β-Induced Pro-Fibrotic Effects in Human Lung Epithelial Cells through Inhibition of Epithelial-Mesenchymal Transition.
1α,25-dihydroxyvitamin D3 Attenuates TGF-β-Induced Pro-Fibrotic Effects in Human Lung Epithelial Cells through Inhibition of Epithelial-Mesenchymal Transition.
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1 α,25-二羟基维生素 D3 通过抑制上皮-间质转化来减弱人肺上皮细胞中 TGF-β 诱导的促纤维化作用
DOI：
10.3390/nu9090980
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发表时间：
2017-09-06
期刊：
影响因子：
5.9
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Jiang F;Yang Y;Xue L;Li B;Zhang Z
肺纤维化是一种进行性纤维化肺部疾病，伴有持续性肺损伤和伤口修复效果不佳，预后较差。肺泡上皮细胞上皮间充质转化（Epithelial-mesenchymal transition， EMT）是肺纤维化发生的早期过程，而转化生长因子β (TGF-β)是公认的EMT诱导因子。流行病学研究表明，血清25-羟基维生素D水平与纤维化疾病的存在有关。我们研究维生素D是否通过抑制人肺泡上皮A549细胞的EMT来减弱TGF-β诱导的促纤维化作用。用TGF-β单独或联合1α，25-二羟基维生素D3 （1α,25(OH)2D3）培养A549细胞。TGF-β升高间质标志物N-cadherin和Vimentin的表达，降低上皮标志物E-cadherin的表达。1α,25(OH)2D3可减弱这些TGF-β诱导的改变。此外，1α,25(OH)2D3抑制了emt相关转录因子（Snail和β-catenin）和细胞外基质基因（Collagen I和纤维连接蛋白）的表达，提高了维生素D受体（VDR）的表达。此外，1α,25(OH)2D3通过抓伤愈合和transwell实验证实，可减轻TGF-β刺激的A549细胞的迁移和侵袭能力。提示1α，25(OH)2D3可抑制TGF-β刺激下肺上皮细胞的促纤维化表型，为肺纤维化的临床治疗提供新的线索。
Pulmonary fibrosis is a progressive fibrotic lung disease of persisting lung injury and ineffective wound repair, with poor prognosis. Epithelial–mesenchymal transition (EMT) of alveolar epithelia cells is an early event in the development of pulmonary fibrosis, and transforming growth factor β (TGF-β) is an acknowledged inducer of EMT. Epidemiological studies demonstrated that serum levels of 25-hydroxy-vitamin D were associated with the presence of fibrosis diseases. We investigated whether vitamin D attenuated TGF-β-induced pro-fibrotic effects through inhibiting EMT in human alveolar epithelia A549 cells. A549 cells were cultured with TGF-β alone or in combination with 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). TGF-β increased the expression of the mesenchymal markers (N-cadherin and Vimentin), and decreased the expression of epithelial markers (E-cadherin). 1α,25(OH)2D3 attenuated these TGF-β-induced alterations. Furthermore, the EMT-related transcription factors (Snail and β-catenin) and the extracellular matrix genes (Collagen I and fibronectin) were inhibited by 1α,25(OH)2D3, while the expression of vitamin D receptor (VDR) was elevated. In addition, 1α,25(OH)2D3 alleviated the cell migration and the invasion abilities in TGF-β-stimulated A549 cells, determined by the scratch wound healing and transwell assays. Our findings suggested that 1α,25(OH)2D3 inhibited the pro-fibrotic phenotype of lung epithelial cells under TGF-β stimulation and provided new clues in the clinical management of pulmonary fibrosis.
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影响因子：
5.8
作者：
Fischer KD;Agrawal DK
通讯作者：
Agrawal DK
影响因子：
13.5
作者：
Petta, Salvatore;Camma, Calogero;Craxi, Antonio
通讯作者：
Craxi, Antonio
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
DOI：
10.1677/joe-08-0241
发表时间：
2009-02
期刊：
The Journal of endocrinology
影响因子：
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作者：
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通讯作者：
Norris KC
影响因子：
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作者：
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通讯作者：
Astor, Brad