母-胎界面RANKL调节滋养细胞生物学行为的分子机制

项目名称： 母-胎界面RANKL调节滋养细胞生物学行为的分子机制

项目编号： No.81501275

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 孟玉菡

作者单位： 潍坊医学院

项目金额： 18万元

中文摘要： RANKL是肿瘤坏死因子（TNF）配体超家族成员，参与多种生理病理过程，如骨重塑、淋巴结形成、胸腺发育、孕期乳腺发育、促进肿瘤的发生和骨转移及中枢体温调节等。本课题组前期研究发现人早孕期绒毛组织及滋养细胞表达RANKL及其受体RANK，并且RANKL促进滋养细胞的增殖及侵袭，但RANKL调节滋养细胞生物学行为的分子机制尚不清楚。本课题拟以RANKL在母-胎界面的表达为切入点，应用实时定量PCR、Transwell小室、质粒转染、SiRNA干扰及western blot技术，探讨RANKL是否通过PI3K/Akt、Erk或NF-κB信号通路，进而调节滋养细胞的侵袭等生物学行为；并利用RANKL基因敲除小鼠研究RANKL在胚胎着床及滋养细胞侵袭中的作用。通过本项目研究有利于阐明RANKL对滋养细胞侵袭能力的调控作用及其分子机制，将为滋养细胞疾病如自然流产等发病机理的研究提供理论基础。

中文关键词： RANKL；母-胎界面；滋养细胞；生物学行为；分子机制

英文摘要： RANKL is a member of tumor necrosis factor superfamily, and it is involved in many physiological and pathological processes, such as bone remodeling, lymph node formation, thymus development, formation of lactating mammary glands, promoting tumorigenesis and bone metastases, controlling fever, and so on. Our recent study found that RANKL and its receptor RANK were expressed in villi and trophoblasts in human early pregnancy, and RANKL promoted the proliferation and invasion of trophoblasts. But the molecular mechanism of RANKL which regulates the biological behavior of trophoblasts is unclear. The project is based on the expression of RANKL at the maternal-fetal interface. We apply real time quantitative PCR, Transwell chamber, plasmid transfection, SiRNA interference and western blotting to explore whether RANKL regulates trophoblasts invasion through PI3K/Akt, Erk or NF-κB signaling pathway. In addition, RANKL knockout mice are used to study the effect of RANKL on embryo implantation. This research is beneficial to clarify the effect of RANKL on trophoblasts invasion and its molecular mechanism, which will provide the theoretical foundation of trophoblastic diseases such as spontaneous abortion.

英文关键词： RANKL ;the maternal-fetal interface ;trophoblasts ;biological behavoir ;molecular mechanism