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下调的JDP2通过Wnt/β-连环蛋白途径抑制上皮-间质转化,从而减弱子痫前期中滋养细胞的侵袭和迁移。

Down-Regulated JDP2 Attenuated Trophoblast Invasion and Migration in Preeclampsia by Inhibiting Epithelial-Mesenchymal Transition through the Wnt/β-Catenin Pathway.

作者信息

Jiang Ziyan, Huang Shiyun, Ying Tingting, Liu Lenan, Han Yufei, Feng Runrun, Sun Haiyan, Cao Ceng, Zuo Qing, Ge Zhiping

机构信息

Department of Obstetrics and Gynaecology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, JiangSu Province, China.

出版信息

Curr Protein Pept Sci. 2025;26(2):156-166. doi: 10.2174/0113892037332988240816052550.

Abstract

INTRODUCTION

Preeclampsia (PE) is an immensely prevalent condition that poses a significant risk to both maternal and fetal health. It is recognized as a primary cause of perinatal morbidity and mortality. Despite extensive research efforts, the precise impact of JDP2 on trophoblast invasion and migration in the context of preeclampsia remains unclear.

MATERIALS AND METHODS

The present study aimed to investigate the differential expression of JDP2 between normal control and preeclampsia placentas through the use of quantitative polymerase chain reaction (qPCR), western blotting, and immunostaining techniques. Furthermore, the effects of JDP2 overexpression and silencing on the migration, invasion, and wound healing capabilities of HTR-8/SVneo cells were evaluated. In addition, this study also examined the impact of JDP2 on epithelial-mesenchymal transition (EMT)-associated biomarkers and the Wnt/β-catenin pathway.

RESULTS

In the present investigation, it was ascertained that Jun dimerization protein 2 (JDP2) exhibited a substantial decrease in expression levels in placentae afflicted with preeclampsia in comparison to those of normal placentae. Impairment in migration and invasion was noted upon JDP2 down-regulation, whereas augmentation of migration and invasion was observed upon JDP2 overexpression in HTR-8/SVneo cells. Subsequently, western blot and immunofluorescence assays were conducted, revealing marked alterations in EMT-associated biomarkers, such as E-cadherin, N-cadherin, and β-catenin, thereby indicating that JDP2 can facilitate cell invasion by modulating the EMT process in HTR-8/SVneo cells. Finally, activation of Wnt/β-catenin signaling was observed as a result of JDP2. After that, IWR-1, a Wnt inhibitor, was used in the recovery study. IWR-1 could inhibit the role of JDP2 in promoting migration and invasion in HTR-8/SVneo cells.

CONCLUSION

Our findings elucidated the impact of JDP2 on trophoblast invasion and migration in preeclampsia by suppressing the EMT through the Wnt/β-catenin signaling pathway, thereby offering a potential prognostic and therapeutic biomarker for this condition.

摘要

引言

子痫前期(PE)是一种极为常见的病症,对孕产妇和胎儿健康构成重大风险。它被认为是围产期发病和死亡的主要原因。尽管进行了广泛的研究,但在子痫前期背景下,JDP2对滋养细胞侵袭和迁移的确切影响仍不清楚。

材料与方法

本研究旨在通过定量聚合酶链反应(qPCR)、蛋白质免疫印迹法和免疫染色技术,研究正常对照胎盘与子痫前期胎盘之间JDP2的差异表达。此外,评估了JDP2过表达和沉默对HTR-8/SVneo细胞迁移、侵袭和伤口愈合能力的影响。此外,本研究还检测了JDP2对上皮-间质转化(EMT)相关生物标志物和Wnt/β-连环蛋白通路的影响。

结果

在本研究中,确定与正常胎盘相比,子痫前期胎盘组织中Jun二聚化蛋白2(JDP2)的表达水平显著降低。JDP2下调时,细胞迁移和侵袭能力受损,而在HTR-8/SVneo细胞中JDP2过表达时,观察到迁移和侵袭能力增强。随后,进行了蛋白质免疫印迹和免疫荧光分析,结果显示EMT相关生物标志物,如E-钙黏蛋白、N-钙黏蛋白和β-连环蛋白发生了显著变化,这表明JDP2可通过调节HTR-8/SVneo细胞中的EMT过程促进细胞侵袭。最后,观察到JDP2激活了Wnt/β-连环蛋白信号通路。之后,在恢复实验中使用了Wnt抑制剂IWR-1。IWR-1可抑制JDP2在促进HTR-8/SVneo细胞迁移和侵袭中的作用。

结论

我们的研究结果阐明了JDP2通过Wnt/β-连环蛋白信号通路抑制EMT,对子痫前期滋养细胞侵袭和迁移的影响,从而为该病症提供了一种潜在的预后和治疗生物标志物。

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