The inhibition of NOTCH2 reduces UVB-induced damage in retinal pigment epithelium cells.
The inhibition of NOTCH2 reduces UVB-induced damage in retinal pigment epithelium cells.
复制标题
抑制 NOTCH2 可减少 UVB 诱导的视网膜色素上皮细胞损伤
DOI：
10.3892/mmr.2017.6625
复制
发表时间：
2017-07
影响因子：
3.4
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Liu L;Zhou X;Kuang X;Long C;Liu W;Tang Y;Liu H;He J;Huang Z;Fan Y;Zhang Q;Shen H
年龄相关性黄斑变性（AMD）是老年人不可逆失明的主要原因。干性 AMD 的发病机制仍不明确，干性 AMD 中视网膜色素上皮 (RPE) 细胞死亡的机制存在争议。本研究的目的是研究 Notch 信号在紫外线 B (UVB) 诱导的 RPE 细胞损伤中的功能。研究发现，在 RPE 细胞中，UVB 增加细胞内活性氧 (ROS) 并诱导细胞凋亡。此外，UVB 以剂量依赖性方式激活 Notch 信号传导。令人惊讶的是，NOTCH2（而不是 NOTCH1）被证明是 RPE 细胞中的主要 Notch 受体。正常情况下，抑制NOTCH2可减少细胞生长和细胞迁移，但对细胞内ROS和细胞凋亡没有影响。然而，在 UVB 存在的情况下，NOTCH2 的抑制（而非 NOTCH1）会减弱细胞内 ROS 和细胞凋亡。 Notch信号在RPE细胞UVB损伤中的作用不仅对于理解AMD（尤其是干性AMD）的发病机制具有重要意义，而且对于设计干性AMD的有效治疗药物也很有用。
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. The pathogenesis of dry AMD remains indistinct and the mechanism of retinal pigment epithelium (RPE) cells death in dry AMD is controversial. The aim of the present study was to investigate the functions of Notch signaling in ultraviolet B (UVB)-induced damage of RPE cells. It was identified that, in RPE cells, UVB increased intracellular reactive oxygen species (ROS) and induced cell apoptosis. In addition, UVB activated Notch signaling in a dose dependent manner. Surprisingly, NOTCH2, but not NOTCH1, was demonstrated to be the major Notch receptor in RPE cells. Under normal conditions, the inhibition of NOTCH2 reduced cell growth and cell migration, but had no impact on intracellular ROS and cell apoptosis. However, in the presence of UVB, the inhibition of NOTCH2, but not NOTCH1, attenuated intracellular ROS and cell apoptosis. The function of Notch signaling involved in UVB damage of RPE cells may not only be significant to understanding the pathogenesis of AMD (especially dry AMD), but also useful for designing effective therapeutic agents for dry AMD.