VE-cadherin enables trophoblast endovascular invasion and spiral artery remodeling during placental development.
VE-cadherin enables trophoblast endovascular invasion and spiral artery remodeling during placental development.
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DOI：
10.7554/elife.77241
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发表时间：
2022-04-29
期刊：
影响因子：
7.7
通讯作者：
Kahn, Mark L.
中科院分区：
文献类型：
--
作者：
Sung, Derek C.;Chen, Xiaowen;Chen, Mei;Yang, Jisheng;Schultz, Susan;Babu, Apoorva;Xu, Yitian;Gao, Siqi;Keller, T. C. Stevenson;Mericko-Ishizuka, Patricia;Lee, Michelle;Yang, Ying;Scallan, Joshua P.;Kahn, Mark L.
在哺乳动物胎盘的形成过程中，滋养层侵入母体蜕膜并重塑螺旋动脉，将母体血液带入胎盘。这一过程被称为血管内侵袭，被认为涉及滋养层细胞对血管内皮细胞（EC）功能特征的采用。然而，血管内侵袭的遗传和分子基础仍然不清楚，滋养层是否以类似的方式利用专门的内皮蛋白来创建血管通道仍然未经测试。血管内皮钙粘蛋白（Vascular endothelial cadherin，VE-）是一种选择性表达的同型粘附蛋白，能促进内皮细胞紧密血管的形成和内皮细胞连接的调节。VE-钙粘蛋白也在侵袭性滋养层细胞中表达，并且是这些细胞血管内侵袭的分子机制的主要候选者。在这里，我们表明，VE-钙粘蛋白是必需的滋养层迁移和血管内侵入到母体蜕膜在小鼠。VE-钙粘蛋白缺乏导致螺旋动脉重塑的丧失，从而导致母体血液流入胎盘的减少、胎儿生长受限和死亡。这些研究确定了在胎盘发育过程中滋养层中VE-钙粘蛋白的非内皮作用，并表明内皮蛋白可能在滋养层中发挥功能独特的作用，而不仅仅是模仿EC中的作用。
During formation of the mammalian placenta, trophoblasts invade the maternal decidua and remodel spiral arteries to bring maternal blood into the placenta. This process, known as endovascular invasion, is thought to involve the adoption of functional characteristics of vascular endothelial cells (ECs) by trophoblasts. The genetic and molecular basis of endovascular invasion remains poorly defined, however, and whether trophoblasts utilize specialized endothelial proteins in an analogous manner to create vascular channels remains untested. Vascular endothelial (VE-)cadherin is a homotypic adhesion protein that is expressed selectively by ECs in which it enables formation of tight vessels and regulation of EC junctions. VE-cadherin is also expressed in invasive trophoblasts and is a prime candidate for a molecular mechanism of endovascular invasion by those cells. Here, we show that VE-cadherin is required for trophoblast migration and endovascular invasion into the maternal decidua in the mouse. VE-cadherin deficiency results in loss of spiral artery remodeling that leads to decreased flow of maternal blood into the placenta, fetal growth restriction, and death. These studies identify a non-endothelial role for VE-cadherin in trophoblasts during placental development and suggest that endothelial proteins may play functionally unique roles in trophoblasts that do not simply mimic those in ECs.