Dickkopf-1 inhibits Wnt3a-induced migration and epithelial-mesenchymal transition of human lens epithelial cells
Dickkopf-1 inhibits Wnt3a-induced migration and epithelial-mesenchymal transition of human lens epithelial cells
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Dickkopf-1抑制Wnt3a诱导的人晶状体上皮细胞迁移和上皮间质转化
DOI：
10.1016/j.exer.2017.06.001
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发表时间：
2017-08-01
影响因子：
3.4
通讯作者：
Bao, Xiuli
中科院分区：
文献类型：
--
作者：
Liu, Tingting;Zhang, Limin;Bao, Xiuli
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) 有助于 PCO。我们之前指出，Wnt3a 诱导人晶状体上皮细胞 (LEC) 的 EMT，并在 PCO 的发展中发挥重要作用。本研究旨在测试Dickkopf-1（Dkkl）对Wnt3a诱导的LEC细胞迁移和EMT的潜在影响，并探讨可能的细胞机制。兔 PCO 模型中 Dkkl 的分泌减少，手术后将 Dkkl 注射到眼睛中可防止 PCO 形成。然后在存在或不存在Dkk1的情况下用Wnt3a转染培养的HLE-B3细胞。 Dkk1 治疗恢复了上皮表型并逆转了 Wnt3a 诱导的 EMT 相关蛋白的表达。 Dkkl抑制LEC迁移和基质金属蛋白酶-1(MMP-1)的表达以及MMP-2和MMP-9的活性。 Dkkl 抑制 B-连环蛋白的核积累，B-连环蛋白是经典 Wnt 信号传导的关键调节因子。我们的结果表明Dkkl抑制Wnt3a诱导的人类LEC的迁移和EMT。研究结果有助于预防 PCO 的形成和发展。 (C) 2017 Elsevier Ltd. 保留所有权利。
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 (Dkkl) on Wnt3a-induced cell migration and the EMT of LECs and to explore possible cellular mechanisms. The secretion of Dkkl was reduced in the rabbit PCO model, and Dkkl 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 Dkkl. Dkk1 treatment restored the epithelial phenotype and reversed the expression of EMT-associated proteins induced by Wnt3a. Dkkl suppressed LEC migration and the expression of matrix metalloproteinase-1 (MMP-1), and the activity of MMP-2 and MMP-9. Dkkl inhibited the nuclear accumulation of B-catenin, which is the key regulator of the canonical Wnt signaling. Our results indicate that Dkkl inhibits Wnt3a-induced migration and the EMT of human LECs. The results contribute to the prevention of PCO formation and development. (C) 2017 Elsevier Ltd. All rights reserved.