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

• Published in: BMC medical genetics Vol. 19; no. 1; p. 166
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.09.2018; BioMed Central; BMC
• Subjects: Adherens junctions; Adult; Age; Birth weight; Blood pressure; Body mass index; Case-Control Studies; Cell adhesion & migration; Cell adhesion molecules; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - immunology; Cesarean Section; Cytotoxicity; Cytotoxicity, Immunologic; Decidua; Decidua - immunology; Decidua - pathology; DNA microarrays; Etiology; Female; Gene expression; Gene Expression Regulation; Genetic aspects; Genetic diversity; Genetic research; Genomes; Gynecology; Health aspects; Health risk assessment; Humans; Hypertension; Immune response; Immunity, Innate; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Measles; Mutation; Natural killer cells; Nectin; Nectin-4; Oligonucleotides; Ovarian cancer; Pathogenesis; Placenta; Pre-eclampsia; Pre-Eclampsia - genetics; Pre-Eclampsia - immunology; Pre-Eclampsia - pathology; Pre-Eclampsia - surgery; Preeclampsia; Pregnancy; Proteins; RNA, Messenger - genetics; RNA, Messenger - immunology; Signal transduction; Task forces; Tight junctions; Trophoblast; Trophoblasts; Trophoblasts - immunology; Trophoblasts - pathology; Womens health; Nectin-4; Trophoblast; Pre-eclampsia
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-018-0681-y

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. 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. 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. 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.