Liu Tingting, Zhang Limin, Wang Yanyan, Zhang Haitao, Li Lin, Bao Xiuli
Department of Ophthalmology, The Affiliated Hospital of Inner Mongolia Medical University, Huhhot, 010050, China.
Department of Ophthalmology, The Affiliated Hospital of Inner Mongolia Medical University, Huhhot, 010050, China.
Exp Eye Res. 2017 Aug;161:43-51. doi: 10.1016/j.exer.2017.06.001. Epub 2017 Jun 3.
Posterior capsular opacification (PCO) is a major post-operative complication of cataract surgery. Epithelial-mesenchymal transition (EMT) contributes to PCO. We previously indicated that Wnt3a induces the EMT of human lens epithelial cells (LECs) and plays an important role in the development of PCO. The present study aimed to test the potential effect of Dickkopf-1 (Dkk1) on Wnt3a-induced cell migration and the EMT of LECs and to explore possible cellular mechanisms. The secretion of Dkk1 was reduced in the rabbit PCO model, and Dkk1 injected into the eyes post-surgical manipulation prevented PCO formation. Cultured HLE-B3 cells were then transfected with Wnt3a in the presence or absence of Dkk1. Dkk1 treatment restored the epithelial phenotype and reversed the expression of EMT-associated proteins induced by Wnt3a. Dkk1 suppressed LEC migration and the expression of matrix metalloproteinase-1 (MMP-1), and the activity of MMP-2 and MMP-9. Dkk1 inhibited the nuclear accumulation of β-catenin, which is the key regulator of the canonical Wnt signaling. Our results indicate that Dkk1 inhibits Wnt3a-induced migration and the EMT of human LECs.The results contribute to the prevention of PCO formation and development.
后囊膜混浊（PCO）是白内障手术的主要术后并发症。上皮-间质转化（EMT）促成了PCO。我们之前指出，Wnt3a诱导人晶状体上皮细胞（LECs）发生EMT，并在PCO的发展中起重要作用。本研究旨在测试Dickkopf-1（Dkk1）对Wnt3a诱导的LECs细胞迁移和EMT的潜在影响，并探索可能的细胞机制。在兔PCO模型中，Dkk1的分泌减少，术后操作时将Dkk1注入眼内可预防PCO形成。然后在有或没有Dkk1的情况下，用Wnt3a转染培养的HLE-B3细胞。Dkk1处理恢复了上皮表型，并逆转了Wnt3a诱导的EMT相关蛋白的表达。Dkk1抑制LECs迁移以及基质金属蛋白酶-1（MMP-1）的表达，以及MMP-2和MMP-9的活性。Dkk1抑制β-连环蛋白的核内积累，而β-连环蛋白是经典Wnt信号的关键调节因子。我们的结果表明，Dkk1抑制Wnt3a诱导的人LECs迁移和EMT。这些结果有助于预防PCO的形成和发展。
