Zeng Shanshui, Pan Yue, Liu Fei, Yin Jiaye, Jiang Min, Long Yan, Zhao Xueqin, Lash Gendie E, Yang Hongling
Department of Laboratory, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, 510623, China.
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, 510623, China.
Biochem Biophys Res Commun. 2021 Oct 30;583:128-134. doi: 10.1016/j.bbrc.2021.10.064.
Preeclampsia (PE) threatens the safety of mothers and fetuses, and its pathogenesis is still unclear. Our previous study has found the relationship between PE and serum Clusterin (CLU). This study aimed to investigate the role of CLU on PE. Firstly, levels of CLU in serum and placental tissue from PE patients and healthy pregnancies were compared. Then, RNA sequencing, cell counting kit-8, matrigel invasion, cell apoptosis, and angiogenesis assay were performed to evaluate the role of CLU on primary isolation trophoblast cells. We found the expression of CLU was increased before the clinical syndrome occurred, whereas its level was positively related to the severity of PE. CLU significantly inhibited the expression of matrix metalloproteinase-9 and Vimentin and enhanced E-cadherin to inhibit epithelial-mesenchymal transition of trophoblast cells, further reducing its migration and invasion. Our results suggested that CLU may play a role in regulating trophoblast invasion and migration during placental development, which may be one of the risk factors for PE.
子痫前期（PE）威胁母婴安全，其发病机制仍不清楚。我们之前的研究发现了PE与血清簇集素（CLU）之间的关系。本研究旨在探讨CLU在PE中的作用。首先，比较了PE患者和正常妊娠孕妇血清及胎盘组织中CLU的水平。然后，进行RNA测序、细胞计数试剂盒-8、基质胶侵袭、细胞凋亡和血管生成分析，以评估CLU对原代分离滋养层细胞的作用。我们发现，在临床综合征出现之前CLU的表达就已升高，而其水平与PE的严重程度呈正相关。CLU显著抑制基质金属蛋白酶-9和波形蛋白的表达，并增强E-钙黏蛋白的表达，从而抑制滋养层细胞的上皮-间质转化，进一步降低其迁移和侵袭能力。我们的结果表明，CLU可能在胎盘发育过程中调节滋养层细胞的侵袭和迁移，这可能是PE的危险因素之一。
