Low Molecular Mass Polypeptide-2 in Human Trophoblast: Over-Expression in Hydatidiform Moles and Possible Role in Trophoblast Cell Invasion
Low Molecular Mass Polypeptide-2 in Human Trophoblast: Over-Expression in Hydatidiform Moles and Possible Role in Trophoblast Cell Invasion
复制标题
人滋养层中的低分子量多肽-2：在葡萄胎中的过度表达及其在滋养层细胞侵袭中的可能作用
DOI：
10.1016/j.placenta.2009.01.005
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发表时间：
2009-04-01
期刊：
影响因子：
3.8
通讯作者：
Wang, H.
中科院分区：
文献类型：
--
作者：
Fu, J. -J.;Lin, P.;Wang, H.
胚胎着床涉及胎盘外滋养细胞（EVTs）侵入子宫。过度活跃的EVT侵袭见于包膜样痣和绒毛膜癌。我们之前已经证明20S蛋白酶体参与小鼠胚胎着床，其作用是通过调节evt中基质金属蛋白酶(MMP)-2和MMP-9的表达和活性来介导的。我们的目的是研究低分子质量多肽-2 (LMP2)，一个20S蛋白酶体的β亚基，是否参与调节人类滋养细胞的侵袭。采集正常人胎盘和葡萄胎患者胎盘，采用免疫组化方法研究LMP2在不同病理状态下滋养层柱（TC）、细胞滋养层细胞（CTB）和合胞滋养层细胞（STB）等不同细胞类型中的表达。此外，我们还利用RNAi和抑制剂在Matrigel侵袭试验系统中检测了LMP2或蛋白酶体对HTR-8/SVneo细胞（人侵袭性外滋养细胞系）侵袭的影响。采用实时PCR和明胶酶谱法检测侵袭相关分子MMP-2和MMP-9的变化。我们发现LMP2在部分葡萄胎和完全葡萄胎TC中的表达高于正常人胎盘TC。此外，LMP2敲除显著减弱IL-1 β诱导的体外细胞侵袭，这是蛋白酶体抑制剂容易诱导的反应。综上所述，20S蛋白酶体β亚基LMP2在葡萄胎滋养细胞中的过度表达可能是其高侵袭性表型的原因之一。2009爱思唯尔有限公司版权所有。
Embryo implantation involves invasion of placental extravillous trophoblast cell (EVTs) into the uterus. Hyperactive EVT invasion occurs in hydatidiform moles and choriocarcinomas. We have previously demonstrated that the 20S proteasome is involved in mouse embryo implantation and its action is mediated via regulating the expression and activities of matrix metalloproteinase (MMP)-2 and MMP-9 in the EVTs. Our objective was to investigate whether low molecular mass polypeptide-2 (LMP2), a beta subunit of the 20S proteasome, is involved in the regulation of human trophoblast invasion. Normal human placentas or placentas from hydatidiform mole patients were collected and the expression of LMP2 in different cell types including trophoblastic column (TC), cytotrophoblast cells (CTB) and syncytiotrophoblast (STB) under different pathological states were studied by immunohistochemical analysis. Furthermore, the effect of LMP2 or proteasome on cell invasion was measured by using RNAi and inhibitors in a Matrigel invasion assay system in HTR-8/SVneo cells, a human invasive extravillous trophoblast cell line. Changes in the invasion-related molecules including MMP-2 and MMP-9 were also examined by using real time PCR and gelatin zymography. We demonstrated that the expression of LMP2 in TC of partial hydatidiform mole and complete hydatidiform mole, is higher than that in TC of normal human placentas. Besides, LMP2 knockdown significantly attenuated IL-1 beta-induced cell invasion in vitro, a response readily induced by proteasome inhibitors. In summary, over-expression of the 20S proteasome beta-subunit LMP2 in trophoblast cells of hydatidiform moles may contribute to its highly invasive phenotype. (C) 2009 Elsevier Ltd. All rights reserved.