title: RhoGDI2 is expressed in human trophoblasts and involved in their migration by inhibiting the activation of RAC1.
abstract: The invasion of placental trophoblast cells into the maternal decidua is an essential aspect of placental embedment. The process of placentation bears several striking similarities to tumor cell metastasis. However, trophoblastic migration during implantation and placentation is stringently controlled both in space and time. RhoGDI2 belongs to a family of Rho guanosine diphosphate dissociation inhibitors (RhoGDIs), and RhoGDI2 is a metastasis suppressor gene and a marker of aggressive human cancer. We evaluated whether RhoGDI2 has a physiological role in embryo implantation, particularly trophoblast migration. The mRNA and protein expression levels of RhoGDI2 were higher in term placentas compared with first-trimester placentas as detected by real-time PCR and Western blot. Immunohistochemical studies indicated that RhoGDI2 localized to the cytotrophoblast layer and extravillous trophoblast in first-trimester placentas and was distributed in the syncytiotrophoblast layers of term placentas. Overexpression of RhoGDI2 in HTR-8/SVneo cells was associated with reduced RAC1-guanosine triphosphate (GTP) levels and inhibited cell migration. Conversely, small interfering RNA-mediated downregulation of RhoGDI2 resulted in significantly increased RAC1-GTP levels. Altered RhoGDI2 expression had no significant effects on cell proliferation. In conclusion, RhoGDI2 inhibits trophoblast cell migration, and this function may involve suppression of RAC1 activation.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
authors.forename: Sishi
authors.initials: S
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Cui
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Li
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.forename: Quan
authors.initials: Q
authors.lastname: Na
authors.forename: Caixia
authors.initials: C
authors.lastname: Liu
mesh_terms: D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D010064:Embryo Implantation / Q000502:physiology; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D010929:Placentation / Q000502:physiology; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology* / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: C569658:ARHGDIB protein, human; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D020830:rac1 GTP-Binding Protein
keywords: RAC1; RhoGDI2; migration; trophoblast