Twist: a regulator of epithelial-mesenchymal transition in lung fibrosis.
Twist: a regulator of epithelial-mesenchymal transition in lung fibrosis.
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扭曲：肺纤维化中上皮 - 间质转变的调节剂。
DOI：
10.1371/journal.pone.0007559
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发表时间：
2009-10-23
期刊：
影响因子：
3.7
通讯作者：
Mora AL
中科院分区：
文献类型：
--
作者：
Pozharskaya V;Torres-González E;Rojas M;Gal A;Amin M;Dollard S;Roman J;Stecenko AA;Mora AL
一些研究表明，病毒感染是IPF和相关的纤维化肺疾病发病机制中的一个重要因素。病毒被认为引起上皮细胞损伤并促进上皮-间充质转化(EMT)，这是一个分化的上皮细胞向间充质表型转化的过程，被认为是肺损伤背景下成纤维细胞的来源。我们已经证明了慢性疱疹病毒感染引起的上皮损伤与小鼠γ-疱疹病毒MHV68和肺纤维化之间的关系。我们假设，在病毒诱导的肺纤维化模型中，EMT是由转录因子Twist的表达驱动的。MHV68体外感染小鼠肺上皮细胞可诱导TWIST和间充质标志物的表达。稳定过表达Twist基因可促进MLE15肺上皮细胞的EMT。在体外感染MHV68后，Twist基因的瞬时下调表达导致上皮细胞表型的保留。与之一致的是，在MHV68感染的小鼠肺上皮细胞中有Twist的高表达，而在模拟感染的小鼠中没有表达。特发性肺纤维化(IPF)患者肺组织肺泡上皮细胞Twist呈强阳性。这些细胞具有EMT的特征，E-钙粘蛋白低表达，间充质标志物N-钙粘蛋白上调。最后，具有高Twist蛋白水平的IPF组织也对疱疹病毒EBV呈阳性。我们得出结论，在病毒诱导的肺纤维化模型中，Twist参与了EMT。我们推测，在某些特发性肺间质纤维化中，γ-疱疹病毒感染EB病毒可能是通过TWIST的表达导致EMT损伤的一个来源。
Several studies have implicated viral infection as an important factor in the pathogenesis of IPF and related fibrotic lung disorders. Viruses are thought to cause epithelial cell injury and promote epithelial-mesenchymal transition (EMT), a process whereby differentiated epithelial cells undergo transition to a mesenchymal phenotype, and considered a source of fibroblasts in the setting of lung injury. We have demonstrated an association between the epithelial injury caused by chronic herpes virus infection with the murine γ-herpes virus, MHV68, and lung fibrosis. We hypothesize that EMT in this model of virus-induced pulmonary fibrosis is driven by the expression of the transcription factor Twist. In vitro MHV68 infection of murine lung epithelial cells induced expression of Twist, and mesenchymal markers. Stable overexpression of Twist promoted EMT in MLE15 lung epithelial cells. Transient knockdown expression of Twist resulted in preservation of epithelial phenotype after in vitro MHV68 infection. In concordance, high expression of Twist was found in lung epithelial cells of MHV68 infected mice, but not in mock infected mice. Alveolar epithelial cells from lung tissue of idiopathic pulmonary fibrosis (IPF) patients were strongly positive for Twist. These cells demonstrated features of EMT with low expression of E-cadherin and upregulation of the mesenchymal marker N-cadherin. Finally, IPF tissue with high Twist protein levels was also positive for the herpesvirus, EBV. We conclude that Twist contributes to EMT in the model of virus-induced pulmonary fibrosis. We speculate that in some IPF cases, γ-herpes virus infection with EBV might be a source of injury precipitating EMT through the expression of Twist.
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DOI：
10.1164/ajrccm.159.4.9807077
发表时间：
1999-04-01
影响因子：
24.7
作者：
Stewart, JP;Egan, JJ;Woodcock, AA
通讯作者：
Woodcock, AA
影响因子：
4.1
作者：
Ryan, JL;Fan, HX;Gulley, ML
通讯作者：
Gulley, ML
影响因子：
11.2
作者：
Alexander, NR;Tran, NL;Heimark, RL
通讯作者：
Heimark, RL
影响因子：
11.2
作者：
Horikawa, Toshiyuki;Yang, Jing;Pagano, Joseph S.
通讯作者：
Pagano, Joseph S.
影响因子：
11.2
作者：
Mironchik, Y;Winnard, PT;Raman, V
通讯作者：
Raman, V