PLAC8, a new marker for human interstitial extravillous trophoblast cells, promotes their invasion and migration
PLAC8, a new marker for human interstitial extravillous trophoblast cells, promotes their invasion and migration
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PLAC8是人间质绒毛外滋养层细胞的新标志物，可促进其侵袭和迁移
DOI：
10.1242/dev.148932
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发表时间：
2018-01-01
期刊：
影响因子：
4.6
通讯作者：
Wang, Hongmei
中科院分区：
文献类型：
--
作者：
Chang, Wen-Lin;Liu, Ya-Wei;Wang, Hongmei
摘要人胎盘滋养层细胞的正常分化是妊娠成功的先决条件，这一过程的失调可能导致恶性妊娠结局，如先兆子痫。寻找不同类型滋养层细胞的特异性标志物对于了解滋养层细胞分化至关重要。在这里，我们报告，胎盘特异性蛋白8（PLAC 8）是专门表达在间质绒毛外滋养层细胞（iEVT）的胎母界面。使用模型系统，包括胎盘绒毛-蜕膜共培养、通过使用原代滋养层细胞或外植体诱导iEVT等，我们发现PLAC 8促进了iEVT的侵袭和迁移。从机制上讲，延时成像，GTdR活性测定，免疫共沉淀和RNA-seq研究表明，PLAC 8增加Cdc 42和Rac 1活性，并进一步诱导在迁移滋养层细胞前缘形成丝状伪足。更有趣的是，PLAC 8在缺氧下显著上调，并且当与来自正常对照胎盘的那些相比时，来自先兆子痫胎盘的iEVT中PLAC 8的表达更高。总之，PLAC 8是iEVT的新标志物，在促进滋养层细胞侵袭和迁移中起重要作用。突出显示的文章：胎盘特异性蛋白8的氧分压依赖性表达部分通过上调Rac 1和Cdc 42的活化来正向调节滋养层细胞的侵袭和迁移。
ABSTRACT Proper differentiation of trophoblast cells in the human placenta is a prerequisite for a successful pregnancy, and dysregulation of this process may lead to malignant pregnancy outcomes, such as preeclampsia. Finding specific markers for different types of trophoblast cells is essential for understanding trophoblast differentiation. Here, we report that placenta-specific protein 8 (PLAC8) is specifically expressed in the interstitial extravillous trophoblast cells (iEVTs) on the fetomaternal interface. Using model systems, including placental villi-decidua co-culture, iEVTs induction by using primary trophoblast cells or explants, etc., we found that PLAC8 promotes invasion and migration of iEVTs. Mechanistically, time-lapse imaging, GTPase activity assay, co-immunoprecipitation and RNA-seq studies show that PLAC8 increases the Cdc42 and Rac1 activities, and further induces the formation of filopodia at the leading edge of the migratory trophoblast cells. More interestingly, PLAC8 is significantly upregulated under hypoxia and expression of PLAC8 is higher in iEVTs from preeclamptic placentas when compared with those from the normal control placentas. Together, PLAC8 is a new marker for iEVTs and plays an important role in promoting trophoblast invasion and migration. Highlighted Article: Oxygen tension-dependent expression of placenta-specific protein 8 positively regulates trophoblast invasion and migration partially through upregulating the activation of Rac1 and Cdc42.