title: Silencing of Paternally Expressed Gene 10 Inhibits Trophoblast Proliferation and Invasion.
abstract: Paternally expressed gene 10 (PEG10) is an imprinted and monoallelic expressed gene. Previous study using a knockout mouse model revealed a crucial role of PEG10 in placental development, yet the exact function of PEG10 during placentation remains to be elucidated. In this study, denuded chorionic villi were prepared from first trimester human placentas, and transduced with PEG10 small interference RNA (siRNA) or non-targeting control sequence by lentiviral infection. Immunohistochemical staining revealed that silencing of PEG10 in the chorionic villous explants resulted in reduced immune-reactivity to CK7, Ki67 and integrin α5, implying that silencing of PEG10 impaired the proliferation of villous trophoblasts and may interfere with the activity of extravillous trophoblasts. We further investigated the role of PEG10 in the proliferation, migration and invasion of JEG-3 trophoblast cell line and the primary chorionic villous cells. PEG10-silenced JEG-3 cells and primary chorionic villous cells displayed a reduced proliferation rate and impaired invasiveness in vitro. Silencing of PEG10 in trophoblast cells led to upregulated expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) as well as downregulated expression of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, knockdown of TIMP-1 reversed the suppressed invasiveness of PEG10 siRNA-transduced JEG-3 cells. In conclusion, our study demonstrates that PEG10 plays an important role in trophoblast proliferation and promotes trophoblast invasion through TIMP-1.
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Manni
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Tong
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Meng
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002824:Chorionic Villi / Q000502:physiology; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D010929:Placentation / Q000235:genetics* / Q000502:physiology; D011247:Pregnancy; D011506:Proteins / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000502:physiology; D014327:Trophoblasts / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C432965:PEG10 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1