Li Yan, Xing Bao-Xiang, Wang Yi-Hao, Yu Sha, Zhao Han, Lv Qing-Qing, Lu Cai-Xia
Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, 266003, Qingdao, Shandong, China.
Department of Pain Medicine, Qingdao Municipal Hospital, 266011, Qingdao, Shandong, China.
J Cell Commun Signal. 2022 Mar;16(1):63-74. doi: 10.1007/s12079-021-00625-3. Epub 2021 May 27.
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.
子痫前期（PE）是一种以高血压为特征的妊娠并发症，与孕产妇和胎儿的高发病率相关。在机制层面，PE的特征是滋养细胞侵袭能力降低。含胶原蛋白三螺旋重复序列-1（CTHRC1）在几种恶性肿瘤中是一种众所周知的肿瘤促进因子，但其在滋养细胞中的作用尚不清楚。在本研究中，我们对来自PE妊娠和正常妊娠的胎盘组织样本中CTHRC1的表达进行了表征。我们使用滋养细胞系HTR-8/SVneo和JEG-3来研究CTHRC1在细胞迁移、侵袭和增殖中的作用。采用蛋白质免疫印迹法、聚合酶链反应和TOP/FOP荧光素酶活性测定法来研究这些细胞行为的分子机制。从患有PE的孕妇获得的胎盘组织样本中CTHRC1的表达水平低于正常妊娠妇女的胎盘组织。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-连环蛋白的核转位，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-连环蛋白信号通路促进滋养细胞的迁移和侵袭。CTHRC1的下调可能是子痫前期发生发展的潜在机制。
