EMT and interstitial lung disease: a mysterious relationship.
EMT and interstitial lung disease: a mysterious relationship.
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DOI：
10.1097/mcp.0b013e3283566721
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发表时间：
2012-09
影响因子：
3.3
通讯作者：
Borok Z
中科院分区：
文献类型：
--
作者：
Kage H;Borok Z
间质性肺疾病（ILD）的发病机制在很大程度上是在最常见的ILD，特发性肺纤维化（IPF）的背景下研究的。我们回顾了上皮细胞向间质细胞转化（EMT）的研究，并讨论了其对IPF中胶原生成（肌）成纤维细胞的潜在作用。内质网（ER）应激导致上皮细胞凋亡已被报道为纤维化的潜在病因。最近的研究进一步表明EMT是ER应激和纤维化之间的联系。Smad 3、β-catenin和其他转录共激活因子在α-平滑肌肌动蛋白（α-SMA）启动子处的组合相互作用为EMT期间转化生长因子-β（TGFβ）和β-catenin途径之间的串扰提供了直接证据。谱系追踪产生了相互矛盾的结果，最近的两项研究支持和反对EMT在肺纤维化中的作用。尽管EMT在体内对肺纤维化的贡献仍存在争议，但在阐明EMT的原因和机制方面取得了进展，可能导致新的治疗选择。除了EMT提供（肌）成纤维细胞的直接来源外，间充质标志物的表达可能反映上皮损伤，在这种情况下，抑制EMT可能是有害的。EMT衍生的细胞也可能有助于促进纤维形成的异常上皮-间充质串扰。
Pathogenesis of interstitial lung diseases (ILD) has largely been investigated in the context of the most frequent ILD, idiopathic pulmonary fibrosis (IPF). We review studies of epithelial to mesenchymal transition (EMT) and discuss its potential contribution to collagen-producing (myo)fibroblasts in IPF. Endoplasmic reticulum (ER) stress leading to epithelial apoptosis has been reported as a potential etiologic factor in fibrosis. Recent studies further suggest EMT as a link between ER stress and fibrosis. Combinatorial interactions among Smad3, β-catenin and other transcriptional co-activators at the α-smooth muscle actin (α-SMA) promoter provide direct evidence for crosstalk between transforming growth factor-β (TGFβ) and β-catenin pathways during EMT. Lineage tracing yielded conflicting results, with two recent studies supporting and one opposing a role for EMT in lung fibrosis. Advances have been made in elucidating causes and mechanisms of EMT, potentially leading to new treatment options, although contributions of EMT to lung fibrosis in vivo remain controversial. In addition to EMT providing a direct source of (myo)fibroblasts, expression of mesenchymal markers may reflect epithelial injury, in which case inhibition of EMT might be deleterious. EMT-derived cells may also contribute to aberrant epithelial-mesenchymal crosstalk that promotes fibrogenesis.