Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Protein and Peptide Science
  4. Volume 26, Issue 2
  5. Article
Volume 26, Issue 2
  • ISSN: 1389-2037
  • E-ISSN: 1875-5550

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.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpps/10.2174/0113892037332988240816052550
2024-08-20
2025-01-22

  • From This Site

    /content/journals/cpps/10.2174/0113892037332988240816052550
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SteegersE.A.P. von DadelszenP. DuvekotJ.J. PijnenborgR. Pre-eclampsia.Lancet2010376974163164410.1016/S0140‑6736(10)60279‑620598363
     [Google Scholar]
  2. RobertsJ.M. CooperD.W. Pathogenesis and genetics of pre-eclampsia.Lancet20013579249535610.1016/S0140‑6736(00)03577‑711197372
     [Google Scholar]
  3. MolB.W.J. RobertsC.T. ThangaratinamS. MageeL.A. de GrootC.J.M. HofmeyrG.J. Pre-eclampsia.Lancet201638710022999101110.1016/S0140‑6736(15)00070‑726342729
     [Google Scholar]
  4. ZárateA. SaucedoR. ValenciaJ. ManuelL. HernándezM. Early disturbed placental ischemia and hypoxia creates immune alteration and vascular disorder causing preeclampsia.Arch. Med. Res.201445751952410.1016/j.arcmed.2014.10.00325450587
     [Google Scholar]
  5. PenningtonK.A. SchlittJ.M. JacksonD.L. SchulzL.C. SchustD.J. Preeclampsia: Multiple approaches for a multifactorial disease.Dis. Model. Mech.20125191810.1242/dmm.00851622228789
     [Google Scholar]
  6. JamesJ.L. WhitleyG.S. CartwrightJ.E. Preeclampsia: Fitting together the placental, immune and cardiovascular pieces.J. Pathol.2010221436337810.1002/path.271920593492
     [Google Scholar]
  7. E DaviesJ. PollheimerJ. YongH.E. KokkinosM.I. KalionisB. KnöflerM. MurthiP. Epithelial-mesenchymal transition during extravillous trophoblast differentiation.Cell Adhes. Migr.201610331032110.1080/19336918.2016.117025827070187
     [Google Scholar]
  8. Red-HorseK. ZhouY. GenbacevO. PrakobpholA. FoulkR. McMasterM. FisherS.J. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface.J. Clin. Invest.2004114674475410.1172/JCI20042299115372095
     [Google Scholar]
  9. KokkinosM.I. MurthiP. WafaiR. ThompsonE.W. NewgreenD.F. Cadherins in the human placenta – Epithelial–mesenchymal transition (EMT) and placental development.Placenta201031974775510.1016/j.placenta.2010.06.01720659767
     [Google Scholar]
  10. KalluriR. WeinbergR.A. The basics of epithelial-mesenchymal transition.J. Clin. Invest.200911961420142810.1172/JCI3910419487818
     [Google Scholar]
  11. RoussosE.T. KeckesovaZ. HaleyJ.D. EpsteinD.M. WeinbergR.A. CondeelisJ.S. AACR special conference on epithelial-mesenchymal transition and cancer progression and treatment.Cancer Res201070197360736410.1158/0008‑5472.CAN‑10‑1208
     [Google Scholar]
  12. KalluriR. EMT: When epithelial cells decide to become mesenchymal-like cells.J. Clin. Invest.200911961417141910.1172/JCI3967519487817
     [Google Scholar]
  13. WeierJ.F. WeierH.U.G. JungC.J. GormleyM. ZhouY. ChuL.W. GenbacevO. WrightA.A. FisherS.J. Human cytotrophoblasts acquire aneuploidies as they differentiate to an invasive phenotype.Dev. Biol.2005279242043210.1016/j.ydbio.2004.12.03515733669
     [Google Scholar]
  14. LalaP.K. LeeB.P. XuG. ChakrabortyC. Human placental trophoblast as an in vitro model for tumor progression.Can. J. Physiol. Pharmacol.200280214214910.1139/y02‑00611934257
     [Google Scholar]
  15. AronheimA. ZandiE. HennemannH. ElledgeS.J. KarinM. Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions.Mol. Cell. Biol.19971763094310210.1128/MCB.17.6.30949154808
     [Google Scholar]
  16. OstrovskyO. BengalE. AronheimA. Induction of terminal differentiation by the c-Jun dimerization protein JDP2 in C2 myoblasts and rhabdomyosarcoma cells.J. Biol. Chem.200227742400434005410.1074/jbc.M20549420012171923
     [Google Scholar]
  17. Bitton-WormsK. PikarskyE. AronheimA. The AP-1 repressor protein, JDP2, potentiates hepatocellular carcinoma in mice.Mol. Cancer2010915410.1186/1476‑4598‑9‑5420214788
     [Google Scholar]
  18. XuY. WuD. JiangZ. ZhangY. WangS. MaZ. HuiB. WangJ. QianW. GeZ. SunL. MiR-616-3p modulates cell proliferation and migration through targeting tissue factor pathway inhibitor 2 in preeclampsia.Cell Prolif.2018515e1249010.1111/cpr.1249030028057
     [Google Scholar]
  19. XuY. GeZ. ZhangE. ZuoQ. HuangS. YangN. WuD. ZhangY. ChenY. XuH. HuangH. JiangZ. SunL. The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic suppression of RND3.Cell Death Dis.2017810e310410.1038/cddis.2017.50329022920
     [Google Scholar]
  20. XuY. WuD. LiuJ. HuangS. ZuoQ. XiaX. JiangY. WangS. ChenY. WangT. SunL. Downregulated lncRNA HOXA11-AS affects trophoblast cell proliferation and migration by regulating RND3 and HOXA7 expression in PE.Mol. Ther. Nucleic Acids20181219520610.1016/j.omtn.2018.05.00730195759
     [Google Scholar]
  21. ZuoQ. HuangS. ZouY. XuY. JiangZ. ZouS. XuH. SunL. The Lnc RNA SPRY4-IT1 modulates trophoblast cell invasion and migration by affecting the epithelial-mesenchymal transition.Sci. Rep.2016613718310.1038/srep3718327853262
     [Google Scholar]
  22. BharadwajS. BhatV.B. VickneswaranV. AdhisivamB. ZachariahB. HabeebullahS. Oxidative stress in preeclamptic mother – Newborn dyads and its correlation with early neonatal outcome – A case control study.J. Matern. Fetal Neonatal Med.201831121548155310.1080/14767058.2017.131993328412854
     [Google Scholar]
  23. DaSilva-ArnoldS.C. ZamudioS. Al-KhanA. Alvarez-PerezJ. MannionC. KoenigC. LukeD. PerezA.M. PetroffM. AlvarezM. IllsleyN.P. Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta.Biol. Reprod.201899240942110.1093/biolre/ioy04229438480
     [Google Scholar]
  24. XuY. XiaX. JiangY. WuD. WangS. FuS. YangN. ZhangY. SunL. Down-regulated lncRNA AGAP2-AS1 contributes to pre-eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype.J. Cell. Mol. Med.20202484557456810.1111/jcmm.1511332150333
     [Google Scholar]
  25. CalicchioR. BuffatC. MathieuJ.R. Ben SalemN. MehatsC. JacquesS. HertigA. BerkaneN. Grevoul-FresquetJ. SimeoniU. PeyssonnauxC. GavardJ. VaimanD. MirallesF. Preeclamptic plasma induces transcription modifications involving the AP-1 transcriptional regulator JDP2 in endothelial cells.Am. J. Pathol.201318361993200610.1016/j.ajpath.2013.08.02024120378
     [Google Scholar]
  26. Hernández-MartínezR. RamkumarN. AndersonK.V. p120-catenin regulates WNT signaling and EMT in the mouse embryo.Proc. Natl. Acad. Sci. USA201911634168721688110.1073/pnas.190284311631371508
     [Google Scholar]
  27. NietoM.A. A snail tale and the chicken embryo.Int J Dev Biol2018621-2-312112610.1387/ijdb.170301mn
     [Google Scholar]
  28. AhsanK. SinghN. RochaM. HuangC. PrinceV.E. Prickle1 is required for EMT and migration of zebrafish cranial neural crest.Dev. Biol.20194481163510.1016/j.ydbio.2019.01.01830721665
     [Google Scholar]
  29. BaikJ. BorgesL. MagliA. ThatavaT. PerlingeiroR.C.R. Effect of endoglin overexpression during embryoid body development.Exp. Hematol.2012401083784610.1016/j.exphem.2012.06.00722728030
     [Google Scholar]
  30. KimI. HurJ. JeongS. HuR represses Wnt/β-catenin-mediated transcriptional activity by promoting cytoplasmic localization of β-catenin.Biochem. Biophys. Res. Commun.20154571657010.1016/j.bbrc.2014.12.05225534855
     [Google Scholar]
  31. BernaudoS. SalemM. QiX. ZhouW. ZhangC. YangW. RosmanD. DengZ. YeG. YangB. VanderhydenB. WuZ. PengC. Cyclin G2 inhibits epithelial-to-mesenchymal transition by disrupting Wnt/β-catenin signaling.Oncogene201635364816482710.1038/onc.2016.1526876206
     [Google Scholar]
  32. JMa PTEN gene induces cell invasion and migration via regulating AKT/GSK-3β/β-catenin signaling pathway in human gastric cancer.Dig. Dis. Sci.2017621234153425
     [Google Scholar]
  33. GracaninA. Timmermans-SprangE.P.M. van WolferenM.E. RaoN.A.S. GrizeljJ. VinceS. HellmenE. MolJ.A. Ligand-independent canonical Wnt activity in canine mammary tumor cell lines associated with aberrant LEF1 expression.PLoS One201496e9869810.1371/journal.pone.009869824887235
     [Google Scholar]
  34. AtalaA. Re: Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry.J. Urol.2016195122022110.1016/j.juro.2015.10.01026699994
     [Google Scholar]
  35. Rapetti-MaussR. BustosV. ThomasW. McBryanJ. HarveyH. LajczakN. MaddenS.F. PellissierB. BorgeseF. SorianiO. HarveyB.J. Bidirectional KCNQ1: β-catenin interaction drives colorectal cancer cell differentiation.Proc. Natl. Acad. Sci. USA2017114164159416410.1073/pnas.170291311428373572
     [Google Scholar]
  36. GuoF. GaoY. SuiG. JiaoD. SunL. FuQ. JinC. miR-375-3p/YWHAZ/β-catenin axis regulates migration, invasion, EMT in gastric cancer cells.Clin. Exp. Pharmacol. Physiol.201946214415210.1111/1440‑1681.1304730353914
     [Google Scholar]
/content/journals/cpps/10.2174/0113892037332988240816052550
Loading
Down-Regulated JDP2 Attenuated Trophoblast Invasion and Migration in Preeclampsia by Inhibiting Epithelial-Mesenchymal Transition through the Wnt/β-Catenin Pathway
Curr. Protein Pept. Sci. 26, 156 (2025); https://doi.org/10.2174/0113892037332988240816052550
/content/journals/cpps/10.2174/0113892037332988240816052550
/content/journals/cpps/10.2174/0113892037332988240816052550
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s web site along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): Epithelial-Mesenchymal Transition (EMT); invasion; Jun dimerization protein 2 (JDP2); migration; Preeclampsia; Wnt/β-catenin pathway

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test