title: Extranuclear Translocation of High-Mobility Group A1 Reduces the Invasion of Extravillous Trophoblasts Involved in the Pathogenesis of Preeclampsia: New Aspect of High-Mobility Group A1.
abstract: High-mobility group A1 (HMGA1) protein is known to express in trophoblast; however, the role of migration has not been reported to date. In this study, we investigated the role of HMGA1 on the pathogenesis of preeclampsia using immortalized human trophoblast cell (HTR-8/SVneo).
  
  
  
  We investigated HMGA1 expression in cytotrophoblasts derived from our preeclampsia model mouse, the CD40L mouse, using immunofluorescence. Wound healing and transwell migration assays were also performed using HTR-8/SVneo (extravillous trophoblast) cells transfected with DNA or siRNA of HMGA1. The effect of extranuclear translocation of HMGA1 on the migration of extravillous trophoblastic cells was evaluated using deoxycholic acid (DCA).
  
  
  
  HMGA1 was expressed exclusively in the nuclei of trophoblasts derived from control mice; cytoplasmic expression was observed only in CD40L mice with preeclampsia. Furthermore, overexpression of HMGA1 in the nuclei of HTR-8/SVneo cells stimulated cell proliferation and migration. Translocation of nuclear HMGA1 to cytoplasm treated with DCA reduced cell migration.
  
  
  
  Collectively, these findings demonstrate that proper subcellular localization of HMGA1 is important for its function in trophoblast cells, and suggest that aberrant cytoplasmic expression of HMGA1 contributes to the pathogenesis of preeclampsia through impairment of trophoblast migration.
authors.affiliation: 1 Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Uchikura
authors.affiliation: 1 Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Matsubara
authors.affiliation: 2 Bell Research Center, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Aichi, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Muto
authors.affiliation: 1 Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsubara
authors.affiliation: 1 Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Fujioka
authors.affiliation: 1 Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: 1 Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D025741:HMGA1a Protein / Q000378:metabolism*; D006801:Humans; D008813:Mice, Inbred ICR; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D025741:HMGA1a Protein
keywords: HTR-8/SVneo; deoxycholic acid; extravillous trophoblast; high-mobility group A1; preeclampsia