Decreased expression of WNT2 in villi of unexplained recurrent spontaneous abortion patients may cause trophoblast cell dysfunction via downregulated Wnt/-catenin signaling pathway
Decreased expression of WNT2 in villi of unexplained recurrent spontaneous abortion patients may cause trophoblast cell dysfunction via downregulated Wnt/-catenin signaling pathway
复制标题
不明原因复发性流产患者绒毛中WNT2表达减少可能通过下调Wnt/-catenin信号通路导致滋养层细胞功能障碍
DOI：
10.1002/cbin.10807
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发表时间：
2017-08-01
影响因子：
3.9
通讯作者：
Liu, Juan
中科院分区：
文献类型：
--
作者：
Li, Ning;Li, Shuhong;Liu, Juan
据报道，WNT 2对胎盘发育，特别是对胎盘的适当血管化是重要的。然而，其在早期妊娠滋养层细胞中的确切作用仍然未知。采用Western blot方法检测不明原因复发性流产（URSA）患者绒毛组织中WNT 2的表达，并与正常对照组进行比较。WNT 2在HTR-8/SVneo滋养层细胞中的功能通过过表达和shRNA敲低改变细胞WNT 2水平来评估。探讨WNT 2对滋养层细胞作用的分子机制。通过Western印迹和免疫荧光研究WNT 2与Wnt/β-catenin信号通路的关联。结果显示，与对照组相比，URSA组绒毛中WNT 2蛋白表达显著降低。体外研究表明，WNT 2可通过激活Wnt/β-catenin信号通路促进人滋养层细胞增殖和迁移。此外，在敲低WNT 2后，滋养层细胞增殖和迁移受到显著抑制。总之，我们的研究表明WNT 2在滋养细胞功能中起着重要作用。WNT 2不足可能通过下调Wnt/β-catenin信号通路导致滋养层细胞增殖和迁移受损。
WNT2 has been reported to be important for placental development, especially for the proper vascularization of the placenta. However, its precise role in first-trimester trophoblast cells is still unknown. WNT2 expression in the villous tissues of unexplained recurrent spontaneous abortion (URSA) patients was compared with that of healthy women by Western blot. The function of WNT2 in HTR-8/SVneo trophoblast cells was evaluated by altering the cellular WNT2 level through overexpression and shRNA knockdown. The molecular mechanism of the effect of WNT2 on trophoblast cells was investigated. The association of WNT2 with the Wnt/-catenin signaling pathway was studied through Western blot and immunofluorescence. Results showed that WNT2 protein expression was significantly decreased in villi of the URSA group compared with the control group. In vitro studies showed that WNT2 could promote human trophoblast cell proliferation and migration through activating the Wnt/-catenin signaling pathway. Moreover, upon the knockdown of WNT2, trophoblast cell proliferation and migration were significantly suppressed. In conclusion, our study indicated that WNT2 plays an important role in trophoblast function. WNT2 insufficiency might cause impaired trophoblast cell proliferation and migration via downregulation of Wnt/-catenin signaling pathway.