Preeclampsia (PE) is a pregnancy complication that is characterized by high blood pressure and is associated with high maternal and fetal morbidities. At a mechanistic level, PE is characterized by reduced invasion ability of trophoblasts. Collagen triple helix repeat containing-1 (CTHRC1) is a well-known tumor-promoting factor in several malignant tumors, but its role in trophoblasts remains unknown. In this study, we characterized the expression of CTHRC1 in placenta tissue samples from PE pregnancies and from normal pregnancies. We used the trophoblasts cell lines HTR-8/SVneo and JEG-3 to investigate the role of CTHRC1 in cell migration, invasion and proliferation. Western blot, PCR and TOP/FOP luciferase activity assays were used to investigate the molecular mechanisms underlying these cell behaviors. Placenta tissue samples obtained from pregnant women with PE expressed lower levels of CTHRC1 than those of placenta tissues from women with normal pregnancies. Down-regulation of CTHRC1 impaired cell proliferation, migration and invasion of trophoblasts, while CTHRC1 overexpression promoted nuclear translocation of β-catenin, a result that was further confirmed by TOP/FOP luciferase activity assay. Our findings suggest that CTHRC1 promotes migration and invasion of trophoblasts via reciprocal Wnt/β-catenin signaling pathway. Down-regulation of CTHRC1 may be a potential mechanism underpinning the development of preeclampsia.

先兆子痫 (PE) 是一种以高血压为特征的妊娠并发症，与母体和胎儿的高发病率有关。在机械水平上，PE 的特点是滋养细胞的侵袭能力降低。胶原蛋白三螺旋重复序列-1 (CTHRC1) 是几种恶性肿瘤中众所周知的促癌因子，但其在滋养细胞中的作用仍然未知。在这项研究中，我们表征了来自 PE 妊娠和正常妊娠的胎盘组织样本中 CTHRC1 的表达。我们使用滋养层细胞系 HTR-8/SVneo 和 JEG-3 来研究 CTHRC1 在细胞迁移、侵袭和增殖中的作用。使用蛋白质印迹、PCR 和 TOP/FOP 荧光素酶活性测定来研究这些细胞行为背后的分子机制。从患有 PE 的孕妇获得的胎盘组织样本表达的 CTHRC1 水平低于来自正常妊娠妇女的胎盘组织样本。CTHRC1 的下调损害了滋养细胞的增殖、迁移和侵袭，而 CTHRC1 的过表达促进了 β-catenin 的核转位，TOP/FOP 荧光素酶活性测定进一步证实了这一结果。我们的研究结果表明，CTHRC1 通过相互的 Wnt/β-catenin 信号通路促进滋养细胞的迁移和侵袭。CTHRC1 的下调可能是支持先兆子痫发展的潜在机制。而 CTHRC1 过表达促进了 β-catenin 的核转位，这一结果通过 TOP/FOP 荧光素酶活性测定得到了进一步证实。我们的研究结果表明，CTHRC1 通过相互的 Wnt/β-catenin 信号通路促进滋养细胞的迁移和侵袭。CTHRC1 的下调可能是支持先兆子痫发展的潜在机制。而 CTHRC1 过表达促进了 β-catenin 的核转位，这一结果通过 TOP/FOP 荧光素酶活性测定得到了进一步证实。我们的研究结果表明，CTHRC1 通过相互的 Wnt/β-catenin 信号通路促进滋养细胞的迁移和侵袭。CTHRC1 的下调可能是支持先兆子痫发展的潜在机制。