Potential role for nectin-4 in the pathogenesis of pre-eclampsia

A molecular genetic study

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number166
JournalBMC Medical Genetics
Volume19
Issue number1
DOIs
Publication statusPublished - 14-09-2018

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Pre-Eclampsia
Molecular Biology
Trophoblasts
Placenta
Adherens Junctions
nectins
Western Blotting
Decidua
Placentation
Pregnancy
Tight Junctions
Cell Adhesion Molecules
Oligonucleotide Array Sequence Analysis
Natural Killer Cells
Real-Time Polymerase Chain Reaction
Cell Membrane
Genome

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

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title = "Potential role for nectin-4 in the pathogenesis of pre-eclampsia: A molecular genetic study",
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.",
author = "Mayuko Ito and Haruki Nishizawa and Makiko Tsutsumi and Asuka Kato and Yoshiko Sakabe and Yoshiteru Noda and Akiko Ohwaki and Jun Miyazaki and Takema Kato and Kazuya Shiogama and Takao Sekiya and Hiroki Kurahashi and Takuma Fujii",
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Potential role for nectin-4 in the pathogenesis of pre-eclampsia : A molecular genetic study. / Ito, Mayuko; Nishizawa, Haruki; Tsutsumi, Makiko; Kato, Asuka; Sakabe, Yoshiko; Noda, Yoshiteru; Ohwaki, Akiko; Miyazaki, Jun; Kato, Takema; Shiogama, Kazuya; Sekiya, Takao; Kurahashi, Hiroki; Fujii, Takuma.

In: BMC Medical Genetics, Vol. 19, No. 1, 166, 14.09.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Potential role for nectin-4 in the pathogenesis of pre-eclampsia

T2 - A molecular genetic study

AU - Ito, Mayuko

AU - Nishizawa, Haruki

AU - Tsutsumi, Makiko

AU - Kato, Asuka

AU - Sakabe, Yoshiko

AU - Noda, Yoshiteru

AU - Ohwaki, Akiko

AU - Miyazaki, Jun

AU - Kato, Takema

AU - Shiogama, Kazuya

AU - Sekiya, Takao

AU - Kurahashi, Hiroki

AU - Fujii, Takuma

PY - 2018/9/14

Y1 - 2018/9/14

N2 - 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.

AB - 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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