Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Clinical Laboratory, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
J Biochem Mol Toxicol. 2020 Apr;34(4):e22454. doi: 10.1002/jbt.22454. Epub 2020 Jan 24.
Dysfunction of trophoblast metastasis into the endometrium is the main cause of pre-eclampsia (PE); however, the factors affecting this process are still unclear. In this study, we found that endoplasmic reticulum protein 29 (ERp29), one molecular chaperone of the endoplasmic reticulum, was aberrantly upregulated in the placenta of pre-eclamptic patients compared with healthy controls. Then, an in vitro study using human extravillous trophoblast HTR-8/SVneo cells showed that ERp29 upregulation could inhibit the migratory and invasive ability of HTR-8/SVneo cells, while ERp29 downregulation had the opposite effect. Mechanical experiments confirmed that ERp29 blocked trophoblast metastasis via inhibiting the process of epithelial-mesenchymal transition and affecting the Wnt/β-catenin signaling pathway. In conclusion, this study revealed the important role of ERp29 in trophoblast metastasis and improved the mechanical understanding of PE occurrence.
滋养层细胞向子宫内膜转移功能障碍是子痫前期(PE)的主要原因;然而,影响这一过程的因素仍不清楚。在这项研究中,我们发现内质网蛋白 29(ERp29),内质网的一种分子伴侣,在子痫前期患者的胎盘组织中异常上调,与健康对照组相比。然后,体外研究使用人绒毛外滋养层 HTR-8/SVneo 细胞表明,ERp29 上调可以抑制 HTR-8/SVneo 细胞的迁移和侵袭能力,而 ERp29 下调则有相反的效果。力学实验证实,ERp29 通过抑制上皮-间充质转化过程和影响 Wnt/β-catenin 信号通路来阻断滋养层细胞的转移。总之,这项研究揭示了 ERp29 在滋养层细胞转移中的重要作用,并提高了对 PE 发生的力学理解。