通过Wnt/β-Catenin通路抑制上皮-间质转化,下调JDP2可减轻子痫前期滋养层细胞的侵袭和迁移

IF 1.9 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current protein & peptide science Pub Date : 2024-08-20 DOI:10.2174/0113892037332988240816052550
Ziyan Jiang, Shiyun Huang, Tingting Ying, Lenan Liu, Yufei Han, Runrun Feng, Haiyan Sun, Ceng Cao, Qing Zuo, Zhiping Ge
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引用次数: 0

摘要

导言:子痫前期(PE)是一种发病率极高的疾病,对产妇和胎儿的健康都有很大风险。它被认为是围产期发病率和死亡率的主要原因。尽管进行了大量研究,但 JDP2 对子痫前期滋养细胞侵袭和迁移的确切影响仍不清楚:本研究旨在通过使用定量聚合酶链反应(qPCR)、Western 印迹和免疫染色技术研究 JDP2 在正常对照和子痫前期胎盘中的不同表达。此外,还评估了 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,本研究还考察了 JDP2 对上皮-间质转化(EMT)相关生物标志物和 Wnt/β-catenin 通路的影响:本研究发现,与正常胎盘相比,子痫前期胎盘中Jun二聚化蛋白2(JDP2)的表达水平大幅下降。下调JDP2后,HTR-8/SVneo细胞的迁移和侵袭能力受损,而过表达JDP2后,迁移和侵袭能力增强。随后进行的 Western 印迹和免疫荧光检测显示,E-cadherin、N-cadherin 和 β-catenin 等 EMT 相关生物标记物发生了明显变化,从而表明 JDP2 可通过调节 HTR-8/SVneo 细胞的 EMT 过程来促进细胞侵袭。最后,JDP2还激活了Wnt/β-catenin信号。随后,在复原研究中使用了一种 Wnt 抑制剂 IWR-1。IWR-1可以抑制JDP2在促进HTR-8/SVneo细胞迁移和侵袭中的作用:我们的研究结果阐明了JDP2通过Wnt/β-catenin信号通路抑制EMT对子痫前期滋养层细胞侵袭和迁移的影响,从而为该病症提供了一个潜在的预后和治疗生物标志物。
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Down-Regulated JDP2 Attenuated Trophoblast Invasion and Migration in Preeclampsia by Inhibiting Epithelial-Mesenchymal Transition through the Wnt/β-Catenin Pathway.

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.

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来源期刊
Current protein & peptide science
Current protein & peptide science 生物-生化与分子生物学
CiteScore
5.20
自引率
0.00%
发文量
73
审稿时长
6 months
期刊介绍: Current Protein & Peptide Science publishes full-length/mini review articles on specific aspects involving proteins, peptides, and interactions between the enzymes, the binding interactions of hormones and their receptors; the properties of transcription factors and other molecules that regulate gene expression; the reactions leading to the immune response; the process of signal transduction; the structure and function of proteins involved in the cytoskeleton and molecular motors; the properties of membrane channels and transporters; and the generation and storage of metabolic energy. In addition, reviews of experimental studies of protein folding and design are given special emphasis. Manuscripts submitted to Current Protein and Peptide Science should cover a field by discussing research from the leading laboratories in a field and should pose questions for future studies. Original papers, research articles and letter articles/short communications are not considered for publication in Current Protein & Peptide Science.
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