Adrenomedullin regulates human placental cell invasion

• Main Authors: Pui-Sze Ng, 吳佩斯
• Other Authors: Hung-Wen Chen
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/56607861177071207586

碩士 === 國立臺灣大學 === 生化科學研究所 === 105 === Invasion of human extravillous trophoblast (EVT) into the maternal endometrium in the early stages of pregnancy is a crucial process of placental development. Human glia cell missing 1 (GCM1) is placenta-specific transcription factor, which plays important roles in regulation of trophoblast differentiation and fusion. Our recent ChIP-chip experiments have demonstrated that GCM1 promotes trophoblast cell invasion via transactivation of HtrA4 and SYDE1 gene expression. Along this line, we have identified adrenomedullin (ADM) as a potential GCM1 target gene. ADM belongs to the calcitonin gene related peptide (CGRP) superfamily, and is widely expressed in human reproductive tissues. To better understand the mechanism of EVT invasion, we studied whether GCM1 also regulates placental cell invasion through ADM. In cell invasion assay, we observed that treatment with ADM significantly enhanced the invasion activity of placental JAR cells, which exhibit low endogenous levels of GCM1 and ADM. In contrast, ADM-knockdown suppressed the invasion activity of placental BeWo cells, which exhibit high endogenous levels of GCM1 and ADM. Furthermore, we demonstrated ADM may stimulate plascental cell invasion through upregulation of transglutaminase 2 (TG2) expression. By co-culture of tetracycline-inducible ADM-expressing JAR cells with decidualized T-HESC monolayer, we also demonstrated enhanced ADM-mediated JAR cell migration in the presence of doxycycline. Our study reveals a novel GCM1-ADM axis in regulation of trophoblast cell invasion and trophoblast-decidual cell interaction during placental development.