Department of Ophthalmology, The Affiliated Ningbo Eye Hospital of Wenzhou Medical University, Ningbo, Zhejiang, China.
Bioengineered. 2022 Jun;13(6):14357-14367. doi: 10.1080/21655979.2022.2085391.
Epithelial-melancholy transition (EMT) is the main cause of organ fibrosis and a common pathogenetic mechanism in most cataracts. This study aimed to explore the molecular mechanism of Toll-like receptor (TLR)-3 in the occurrence and development of post-cataract EMT and to provide new ideas for the prevention and treatment of posterior capsule opacification (PCO). In the presence or absence of TLR3, the human lens epithelial cell (LEC) line, SRA01/04, was treated with the transforming growth factor (TGF)-β2. Cell counting kit-8 (CCK-8) and Transwell assays were used to analyze the cell proliferation, migration, and invasion. The expression levels of proteins and RNAs were detected by western blotting and quantitative polymerase chain reaction (qPCR) experiments. Functional gain and loss studies showed that TLR3 regulates the proliferation, migration, and invasion of LECs and EMT induced by TGF-β2. Moreover, TLR3 regulates the expression of Jagged-1, Notch-1, and Notch-3 These findings indicate that TLR3 prevents the progression of lens fibrosis by targeting the Jagged-1/Notch signaling pathway to regulate the proliferation, migration, and invasion of LECs, and TGF-β2-induced EMT. Therefore, the TLR3-Jagged-1/Notch signaling axis may be a potential therapeutic target for the treatment of fibrotic cataracts.
上皮-黑色素细胞转化（EMT）是器官纤维化的主要原因，也是大多数白内障的共同发病机制。本研究旨在探讨 Toll 样受体（TLR）-3 在白内障后 EMT 发生发展中的分子机制，为预防和治疗后发性白内障（PCO）提供新的思路。在存在或不存在 TLR3 的情况下，用转化生长因子（TGF）-β2 处理人晶状体上皮细胞（LEC）系 SRA01/04。用细胞计数试剂盒-8（CCK-8）和 Transwell 分析细胞增殖、迁移和侵袭。通过 Western blot 和定量聚合酶链反应（qPCR）实验检测蛋白质和 RNA 的表达水平。功能增益和缺失研究表明，TLR3 调节 TGF-β2 诱导的 LEC 增殖、迁移和 EMT。此外，TLR3 调节 Jagged-1、Notch-1 和 Notch-3 的表达。这些发现表明，TLR3 通过靶向 Jagged-1/Notch 信号通路来调节 LEC 的增殖、迁移和侵袭，从而阻止晶状体纤维化的进展，抑制 TGF-β2 诱导的 EMT。因此，TLR3-Jagged-1/Notch 信号轴可能是治疗纤维性白内障的潜在治疗靶点。
