Silencing of Paternally Expressed Gene 10 Inhibits Trophoblast Proliferation and Invasion.
Silencing of Paternally Expressed Gene 10 Inhibits Trophoblast Proliferation and Invasion.
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沉默的亲子表达基因10抑制了滋养细胞的增殖和侵袭。
DOI：
10.1371/journal.pone.0144845
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Meng T
中科院分区：
文献类型：
--
作者：
Chen H;Sun M;Liu J;Tong C;Meng T
父本表达基因 10 (PEG10) 是一种印记单等位基因表达基因。先前使用基因敲除小鼠模型的研究揭示了 PEG10 在胎盘发育中的关键作用，但 PEG10 在胎盘形成过程中的确切功能仍有待阐明。在本研究中，从妊娠早期的人胎盘中制备裸露的绒毛膜绒毛，并通过慢病毒感染转导PEG10小干扰RNA（siRNA）或非靶向控制序列。免疫组织化学染色显示，绒毛膜绒毛外植体中 PEG10 的沉默导致对 CK7、Ki67 和整合素 α5 的免疫反应性降低，这意味着 PEG10 的沉默损害了绒毛滋养细胞的增殖，并可能干扰绒毛外滋养细胞的活性。我们进一步研究了PEG10在JEG-3滋养层细胞系和初级绒毛膜绒毛细胞增殖、迁移和侵袭中的作用。 PEG10 沉默的 JEG-3 细胞和原代绒毛膜绒毛细胞在体外表现出增殖率降低和侵袭性受损。滋养层细胞中 PEG10 的沉默导致金属蛋白酶组织抑制剂-1 (TIMP-1) 的表达上调以及基质金属蛋白酶 (MMP)-2 和 MMP-9 的表达下调。此外，TIMP-1 的敲低逆转了 PEG10 siRNA 转导的 JEG-3 细胞的受抑制的侵袭性。总之，我们的研究表明，PEG10 在滋养层增殖中发挥重要作用，并通过 TIMP-1 促进滋养层侵袭。
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.