Direct involvement of HERV-W env glycoprotein in human trophoblast cell fusion and differentiation
Direct involvement of HERV-W env glycoprotein in human trophoblast cell fusion and differentiation
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DOI：
10.1128/mcb.23.10.3566-3574.2003
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发表时间：
2003-05-01
影响因子：
5.3
通讯作者：
Mallet, F
中科院分区：
文献类型：
--
作者：
Frendo, JL;Olivier, D;Mallet, F
我们最近证明了HERV-W env基因的产物，一种逆转录病毒包膜蛋白，也被称为合胞素，是一种高度融合的膜糖蛋白，在与D型哺乳动物逆转录病毒受体相互作用时诱导合胞体的形成。此外，在胎盘组织切片中检测HERV-W Env蛋白（Env-W）表达使我们提出了这种融合糖蛋白在胎盘形成中的作用。为了评估这一假设，我们分析了参与Env-W在人绒毛细胞滋养层细胞的原代培养物的分化，自发分化的细胞融合成合胞体滋养层细胞在体外。首先，我们观察到HERV-W env mRNA和糖蛋白表达与初级细胞滋养层分化和人绒毛膜促性腺激素（hCG）（合胞体滋养层形成的标志物）的表达共线性。第二，我们观察到，在体外刺激滋养层细胞的融合和分化的环AMP也与HERV-W env和hCG mRNA和蛋白表达的伴随增加。最后，通过使用特定的反义寡核苷酸，我们证明了抑制Env-W蛋白的表达导致滋养层细胞融合和分化的减少，在反义寡核苷酸处理的细胞的培养基中hCG的分泌减少了五倍。总之，这些结果强烈支持Env-W在人滋养层细胞融合和分化中的直接作用。
We recently demonstrated that the product of the HERV-W env gene, a retroviral envelope protein also dubbed syncytin, is a highly fusogenic membrane glycoprotein inducing the formation of syncytia on interaction with the type D mammalian retrovirus receptor. In addition, the detection of HERV-W Env protein (Env-W) expression in placental tissue sections led us to propose a role for this fusogenic glycoprotein in placenta formation. To evaluate this hypothesis, we analyzed the involvement of Env-W in the differentiation of primary cultures of human villous cytotrophoblasts that spontaneously differentiate by cell fusion into syncytiotrophoblasts in vitro. First, we observed that HERV-W env mRNA and glycoprotein expression are colinear with primary cytotrophoblast differentiation and with expression of human chorionic gonadotropin (hCG), a marker of syncytiotrophoblast formation. Second, we observed that in vitro stimulation of trophoblast cell fusion and differentiation by cyclic AMP is also associated with a concomitant increase in HERV-W env and hCG mRNA and protein expression. Finally, by using specific antisense oligonucleotides, we demonstrated that inhibition of Env-W protein expression leads to a decrease of trophoblast fusion and differentiation, with the secretion of hCG in culture medium of antisense oligonucleotide-treated cells being decreased by fivefold. Taken together, these results strongly support a direct role for Env-W in human trophoblast cell fusion and differentiation.