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Open Access 01-12-2018 | Research article

Potential role for nectin-4 in the pathogenesis of pre-eclampsia: a molecular genetic study

Authors: Mayuko Ito, Haruki Nishizawa, Makiko Tsutsumi, Asuka Kato, Yoshiko Sakabe, Yoshiteru Noda, Akiko Ohwaki, Jun Miyazaki, Takema Kato, Kazuya Shiogama, Takao Sekiya, Hiroki Kurahashi, Takuma Fujii

Published in: BMC Medical Genetics | Issue 1/2018

Abstract

Background

Nectins are cell adhesion molecules that play a pivotal role in adherens junctions and tight junctions. Our previous study using whole-genome oligonucleotide microarrays revealed that nectin-4 was upregulated in pre-eclamptic placentas. We investigated the role of nectin-4 in the etiology of pre-eclampsia.

Methods

We investigated the expression of nectin-4 using real-time RT–PCR, western blot and immunostaining. Additionally, we performed matrigel invasion assay and cytotoxicity assay using cells overexpressing the nectin-4.

Results

NECTIN4 transcripts were elevated in pre-eclamptic placentas relative to uncomplicated pregnancies. Nectin-4 protein levels in pre-eclamptic placentas were higher on a semi-quantitative western blot. Nectin-4 was localized at the apical cell membrane in syncytiotrophoblast cells and not at the adherens junctions. Nectin-4 was also detected in cytotrophoblasts and a subset of cells in the decidua. Nectin-4 overexpressing trophoblast cells migrated normally in the matrix. However, Natural killer (NK) cells showed a strong cytotoxic effect against nectin-4 overexpressing trophoblast cells. No causative genetic variation was evident in the NECTIN4 gene from a pre-eclamptic placenta.

Conclusions

There are as yet unknown factors that induce nectin-4 overexpression in trophoblast cells that may contribute to abnormal placentation via an aberrant immune response and the onset of a pre-eclamptic pregnancy.

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Title: Potential role for nectin-4 in the pathogenesis of pre-eclampsia: a molecular genetic study
Authors: Mayuko Ito
Haruki Nishizawa
Makiko Tsutsumi
Asuka Kato
Yoshiko Sakabe
Yoshiteru Noda
Akiko Ohwaki
Jun Miyazaki
Takema Kato
Kazuya Shiogama
Takao Sekiya
Hiroki Kurahashi
Takuma Fujii
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-018-0681-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Potential role for nectin-4 in the pathogenesis of pre-eclampsia: a molecular genetic study

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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