滋养层
生物
细胞融合
细胞生物学
合胞滋养细胞
染色质免疫沉淀
下调和上调
胎盘
细胞
癌症研究
基因表达
胎儿
怀孕
遗传学
基因
发起人
作者
Liangjie Wang,Mei‐Leng Cheong,Yun‐Shien Lee,Ming-Ting Lee,Hung−Wen Chen
摘要
Cell-cell fusion and cell invasion are essential for placental development. Human cytotrophoblasts in the chorionic villi may undergo cell-cell fusion to form syncytiotrophoblasts to facilitate nutrient-gas exchange or differentiate into extravillous trophoblasts (EVTs) to facilitate maternal-fetal circulation. The placental transcription factor glial cells missing 1 (GCM1) regulates syncytin-1 and -2 expression to mediate trophoblast fusion. Interestingly, GCM1 and syncytin-1 are also expressed in EVTs with unknown physiological functions. In this study, we performed chromatin immunoprecipitation-on-chip (ChIP-chip) analysis and identified the gene for high-temperature requirement protein A4 (HtrA4) as a GCM1 target gene, which encodes a serine protease facilitating cleavage of fibronectin and invasion of placental cells. Importantly, HtrA4 is immunolocalized in EVTs at the maternal-fetal interface, and its expression is decreased by hypoxia and in preeclampsia, a pregnancy complication associated with placental hypoxia and shallow trophoblast invasion. We further demonstrate that HtrA4 interacts with syncytin-1 and suppresses cell-cell fusion. Therefore, HtrA4 may be crucial for EVT differentiation by playing a dual role in prevention of cell-cell fusion of EVTs and promotion of their invasion into the uterus. Our study reveals a novel function of GCM1 and HtrA4 in regulation of trophoblast invasion and that abnormal HrtA4 expression may contribute to shallow trophoblast invasion in preeclampsia.
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