The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029, China.
Eur J Cell Biol. 2012 Sep;91(9):728-37. doi: 10.1016/j.ejcb.2012.03.008. Epub 2012 May 16.
When rhegmatogenous retinal detachment occurs, tumor necrosis factor-alpha (TNF-α) among other cytokines leaks into the subretinal space, induces resident retinal pigment epithelial (RPE) cells to migrate, which is the initial step of proliferative vitreoretinopathy (PVR). In the current study, we aim to understand how this is regulated by focusing the cellular mechanisms involved. Here we identified an Akt/Tuberous sclerosis protein 2 (TSC2)/mTOR complex1 (mTORC1) signaling pathway after TNF-α treatment to mediate RPE cell migration. Suppression of mTORC1 activation, either by its inhibitor rapamycin, or by activation of its suppressor AMP activated protein kinase (AMPK), inhibited TNF-α-mediated RPE cell migration, while RNA interference (RNAi)-mediated knocking-down of SIN1 or Rictor, two key components of mTOR complex 2 (mTORC2), had no significant effect on TNF-α-induced RPE cell migration. Our data provide initial evidence that TNF-α-mediated in vitro RPE cell migration mainly requires Akt/mTORC1, but not mTORC2 signaling. The results of this study may lead to indentify novel signaling targets against PVR.
当孔源性视网膜脱离发生时，肿瘤坏死因子-α（TNF-α）和其他细胞因子会渗漏到视网膜下腔，诱导驻留的视网膜色素上皮（RPE）细胞迁移，这是增生性玻璃体视网膜病变（PVR）的初始步骤。在本研究中，我们旨在通过关注相关的细胞机制来了解这是如何被调控的。在这里，我们在 TNF-α 处理后鉴定出 Akt/结节性硬化症蛋白 2（TSC2）/哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）信号通路，以介导 RPE 细胞迁移。mTORC1 的激活受到抑制，无论是通过其抑制剂雷帕霉素，还是通过激活其抑制剂 AMP 激活的蛋白激酶（AMPK），都抑制了 TNF-α介导的 RPE 细胞迁移，而 RNA 干扰（RNAi）介导的 SIN1 或 Rictor 的敲低，mTORC2 的两个关键成分，对 TNF-α诱导的 RPE 细胞迁移没有显著影响。我们的数据提供了初步证据，表明 TNF-α 介导的体外 RPE 细胞迁移主要需要 Akt/mTORC1，而不是 mTORC2 信号。这项研究的结果可能会导致针对 PVR 的新型信号靶点的鉴定。
