骨桥蛋白在子宫内膜的表达调节及对蜕膜化功能的影响

项目名称： 骨桥蛋白在子宫内膜的表达调节及对蜕膜化功能的影响

项目编号： No.81471456

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 谢青贞

作者单位： 武汉大学

项目金额： 73万元

中文摘要： 蜕膜化是胚胎着床及早期胚胎存活所必需的，其典型特征是子宫内膜基质细胞的增殖和分化，同时伴随着新生血管形成，蜕膜化缺陷可导致着床失败或不良妊娠结局。骨桥蛋白(OPN)是一种多功能的细胞外基质糖蛋白，研究提示OPN与子宫蜕膜化和胚胎生长发育有关，但机制还不清楚。本项目拟建立人子宫内膜基质细胞体外诱导蜕膜化模型和小鼠体内、体外研究模型，采用RNA过表达和干涉技术，结合生物信息学算法，利用启动子分析、染色质免疫共沉淀和靶基因验证等方法，研究在着床和蜕膜化过程起重要作用的转录因子cAMP反应元件结合蛋白、CCAAT增强子结合蛋白β以及Micro RNA181a/b对子宫内膜OPN表达的调节，并探讨OPN在子宫内膜容受性的建立、蜕膜化、血管形成及在胚胎发育的功能。研究结果将有助于了解胚胎着床的分子机理。

中文关键词： 骨桥蛋白；蜕膜化；血管形成；微小RNA；转录因子

英文摘要： Decidualization is essential for implantation and early embryo survival during pregnancy, which is characterized by endometrial stromal cells proliferation and differentiation, along with the neovascularization. Decidualization deficiency may lead to implantation failure or even adverse pregnancy outcome. Osteopontin (OPN), a kind of multifunctional matricellular glycoprotein, has been shown to be involved in decidualization and embryonic development, but the underlying mechanisms has not been clear.In this study,we are intend to establish the in vitro decidualization model of human endometrial stromal cells, as well as in vivo and in vitro mouse decidualization models,combining with gene overexpression, RNA interfering, bioinformatics algorithms, promoter analysis, chromatin immunoprecipitation and target gene verification,to revel whether OPN expression in decidua is regulated by the transcriptional factor cAMP-responsive element binding protein(CREB), CCAAT enhancer-binding proteinβ(CEBPβ)and micro RNA181a/b, for further understanding the mutifunction of OPN in uterine receptivity, angiopoiesis and embryo evelopment. This study will provide new insights into the molecular mechanisms underlying embryo implantation.

英文关键词： Osteopontin;decidualization;angiogenesis;Micro RNA;transcriptional factor