The proprotein convertase furin is required for trophoblast syncytialization.
The proprotein convertase furin is required for trophoblast syncytialization.
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滋养层合胞化需要前蛋白转化酶弗林蛋白酶
DOI：
10.1038/cddis.2013.106
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发表时间：
2013-04-18
影响因子：
9
通讯作者：
Wang, H.
中科院分区：
文献类型：
--
作者：
Zhou, Z.;Zhang, Q.;Lu, X.;Wang, R.;Wang, H.;Wang, Y-L;Zhu, C.;Lin, H-Y;Wang, H.
多核合胞体滋养层形成胎盘的最外层并具有多种功能，由细胞滋养层细胞融合分化并维持。合胞滋养层分化或维持的缺陷可能导致宫内生长受限和先兆子痫，这两种常见的妊娠疾病。滋养层细胞合胞化的细胞和分子机制知之甚少。我们在这里报告说，前蛋白转化酶弗林蛋白酶是高度表达的合胞滋养层在孕早期的人类胎盘，和弗林蛋白酶的表达在合体滋养层显着降低在胎盘从先兆子痫患者相比，其胎龄匹配的控制胎盘。使用多个实验模型，包括绒毛膜癌BeWo细胞的诱导融合和原代培养的细胞滋养层细胞或胎盘外植体的自发融合，我们证明，细胞滋养层细胞融合和合胞化是伴随着弗林蛋白酶的表达。弗林蛋白酶特异性siRNA或抑制剂抑制BeWo细胞中的细胞融合以及人胎盘外植体中的滋养层合胞化。此外，1型IGF受体（IGF1R）在这项研究中被指示作为弗林蛋白酶的底物，并且弗林蛋白酶对IGF1R的加工是合胞化的重要机制。最后，使用慢病毒介导的RNAi靶向小鼠滋养外胚层，我们证明，弗林蛋白酶的功能是所需的迷宫层中的合胞体滋养层结构的发展，以及正常的胚胎发育。
The multinucleated syncytial trophoblast, which forms the outermost layer of the placenta and serves multiple functions, is differentiated from and maintained by cytotrophoblast cell fusion. Deficiencies in syncytial trophoblast differentiation or maintenance likely contribute to intrauterine growth restriction and pre-eclampsia, two common gestational diseases. The cellular and molecular mechanisms governing trophoblast syncytialization are poorly understood. We report here that the proprotein convertase furin is highly expressed in syncytial trophoblast in the first trimester human placentas, and expression of furin in the syncytiotrophoblast is significantly lower in the placentas from pre-eclamptic patients as compared with their gestational age-matched control placentas. Using multiple experimental models including induced fusion of choriocarcinoma BeWo cells and spontaneous fusion of primary cultured cytotrophoblast cells or placental explants, we demonstrate that cytotrophoblast cell fusion and syncytialization are accompanied by furin expression. Furin-specific siRNAs or inhibitors inhibit cell fusion in BeWo cells, as well as trophoblast syncytialization in human placental explants. Furthermore, type 1 IGF receptor (IGF1R) is indicated in this study as a substrate of furin, and processing of IGF1R by furin is an essential mechanism for syncytialization. Finally, using lentivirus-mediated RNAi targeting to mouse trophectoderm, we demonstrate that furin function is required for the development of syncytiotrophoblast structure in the labyrinth layer, as well as for normal embryonic development.
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DOI：
10.1016/s1071-5576(01)00134-4
发表时间：
2001-11-01
期刊：
JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION
影响因子：
--
作者：
Crocker, IP;Strachan, BK;Baker, PN
通讯作者：
Baker, PN
影响因子：
8.3
作者：
Li, HS;Dakour, J;Morrish, DW
通讯作者：
Morrish, DW
影响因子：
12.4
作者：
Baczyk, D.;Drewlo, S.;Kingdom, J.
通讯作者：
Kingdom, J.
泛素连接酶 Cullin 7 诱导人绒毛膜癌细胞上皮-间质转化
影响因子：
4.8
作者：
Fu, Jiejun;Lv, Xiaoyin;Wang, Hongmei
通讯作者：
Wang, Hongmei
DOI：
10.1073/pnas.1011293108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Kumasawa, Keiichi;Ikawa, Masahito;Okabe, Masaru
通讯作者：
Okabe, Masaru