title: Human exosomal placenta-associated miR-517a-3p modulates the expression of PRKG1 mRNA in Jurkat cells.
abstract: During pregnancy, human placenta-associated microRNAs (miRNAs) derived from the miRNA cluster in human chromosome 19 are expressed in villous trophoblasts and secreted into maternal circulation via exosomes; however, little is known about whether circulating placenta-associated miRNAs are transferred into maternal immune cells via exosomes, and modulate expression of target genes in the recipient cells. We employed an in vitro model of trophoblast-immune cell communication using BeWo cells (a human trophoblast cell line) and Jurkat cells (a human leukemic T-cell line) and investigated whether BeWo exosomal placenta-associated miRNAs can suppress expression of target genes in the recipient Jurkat cells. Using this system, we identified PRKG1 as a target gene of placenta-associated miRNA miR-517a-3p. Moreover, we demonstrated that BeWo exosomal miR-517a-3p was internalized into Jurkat cells and subsequently suppressed the expression of PRKG1 in recipient Jurkat cells. Furthermore, using peripheral blood natural killer (NK) cells in vivo, we confirmed that circulating miR-517a-3p was delivered into maternal NK cells as it was into Jurkat cells in vitro. Placenta-associated miR-517a-3p was incorporated into maternal NK cells in the third trimester, and it was rapidly cleared after delivery. Expression levels of miR-517a-3p and its target mRNA PRKG1 were inversely correlated in NK cells before and after delivery. These in vitro and in vivo results suggest that exosome-mediated transfer of placenta-associated miRNAs and subsequent modulation of their target genes occur in maternal NK cells. The present study provides novel insight into our understanding of placenta-maternal communication.
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo, Japan Department of Reproductive Medicine, Perinatology and Gynecologic Oncology, Nippon Medical School, Tokyo, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kambe
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshitake
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yuge
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ishida
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo, Japan.
authors.forename: Md Moksed
authors.initials: MM
authors.lastname: Ali
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo, Japan.
authors.forename: Takami
authors.initials: T
authors.lastname: Takizawa
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kuwata
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Ohkuchi
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Reproductive Medicine, Perinatology and Gynecologic Oncology, Nippon Medical School, Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeshita
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Molecular Medicine and Anatomy, Nippon Medical School, Tokyo, Japan t-takizawa@nms.ac.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takizawa
mesh_terms: D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000235:genetics* / Q000378:metabolism; D055354:Exosomes / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D010920:Placenta / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism
chemical_list: C546349:MIRN517 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D062965:Cyclic GMP-Dependent Protein Kinase Type I; C569718:PRKG1 protein, human
keywords: BeWo; Jurkat; PRKG1; exosome; human placenta; microRNA; natural killer cell; regulatory T cell; villous trophoblast