Department of Ophthalmology, Shanghai First People's Hospital, Affiliate of Shanghai Jiaotong University, Shanghai, China.
PLoS One. 2011;6(8):e23322. doi: 10.1371/journal.pone.0023322. Epub 2011 Aug 10.
The proliferation of retinal pigment epithelium (RPE) cells resulting from an epithelial-mesenchymal transition (EMT) plays a key role in proliferative vitreoretinopathy (PVR), which leads to complex retinal detachment and the loss of vision. Genes of Snail family encode the zinc finger transcription factors that have been reported to be essential in EMT during embryonic development and cancer metastasis. However, the function of Snail in RPE cells undergoing EMT is largely unknown.
Transforming growth factor beta(TGF-β)-1 resulted in EMT in human RPE cells (ARPE-19), which was characterized by the expected decrease in E-cadherin and Zona occludin-1(ZO-1) expression, and the increase in fibronectin and α-smooth muscle actin (α-SMA) expression, as well as the associated increase of Snail expression at both mRNA and protein levels. Furthermore, TGF-β1 treatment caused a significant change in ARPE-19 cells morphology, with transition from a typical epithelial morphology to mesenchymal spindle-shaped. More interestingly, Snail silencing significantly attenuated TGF-β1-induced EMT in ARPE-19 cells by decreasing the mesenchymal markers fibronectin and a-SMA and increasing the epithelial marker E-cadherin and ZO-1. Snail knockdown could effectively suppress ARPE-19 cell migration. Finally, Snail was activated in epiretinal membranes from PVR patients. Taken together, Snail plays very important roles in TGF-β-1-induced EMT in human RPE cells and may contribute to the development of PVR.
Snail transcription factor plays a critical role in TGF-β1-induced EMT in human RPE cells, which provides deep insight into the pathogenesis of human PVR disease. The specific inhibition of Snail may provide a new approach to treat and prevent PVR.
视网膜色素上皮（RPE）细胞的增殖导致上皮-间充质转化（EMT），在增生性玻璃体视网膜病变（PVR）中起着关键作用，导致复杂的视网膜脱离和视力丧失。Snail 家族的基因编码锌指转录因子，据报道在胚胎发育和癌症转移的 EMT 中是必不可少的。然而，Snail 在经历 EMT 的 RPE 细胞中的功能在很大程度上是未知的。
转化生长因子-β（TGF-β）-1 导致人 RPE 细胞（ARPE-19）发生 EMT，其特征是 E-钙粘蛋白和 ZO-1 表达预期下降，纤连蛋白和α-平滑肌肌动蛋白（α-SMA）表达增加，以及 Snail 表达在 mRNA 和蛋白质水平上的相关增加。此外，TGF-β1 处理导致 ARPE-19 细胞形态发生显著变化，从典型的上皮形态转变为间充质纺锤形。更有趣的是，Snail 沉默通过降低间充质标志物纤连蛋白和α-SMA，增加上皮标志物 E-钙粘蛋白和 ZO-1，显著减弱 TGF-β1 诱导的 ARPE-19 细胞 EMT。Snail 敲低可有效抑制 ARPE-19 细胞迁移。最后，在 PVR 患者的视网膜前膜中激活了 Snail。综上所述，Snail 在 TGF-β-1 诱导的人 RPE 细胞 EMT 中发挥着非常重要的作用，可能有助于 PVR 的发展。
Snail 转录因子在 TGF-β-1 诱导的人 RPE 细胞 EMT 中起着关键作用，这为人类 PVR 疾病的发病机制提供了深入的了解。Snail 的特异性抑制可能为治疗和预防 PVR 提供新的方法。
