滋养层细胞自噬异常导致原因不明习惯性流产的分子机制研究

项目名称： 滋养层细胞自噬异常导致原因不明习惯性流产的分子机制研究

项目编号： No.81501250

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： 李晓翠

作者单位： 上海交通大学

项目金额： 18万元

中文摘要： 不明原因的习惯性流产是人类妊娠中常见的合并症。研究发现该类疾病的发生常常与滋养层细胞侵袭力不足有关。我们前期的mRNA芯片结果也发现自噬相关基因LC3B和Beclin1基因在原因不明自发性流产患者的滋养层组织表达显著增加。初步的实验结果表明该分子具有调控滋养层细胞的侵袭能力。在此基础上，本课题拟深入研究LC3B和Beclin1调控滋养层细胞侵袭的分子机制。本项目检测LC3B和Beclin1对参与滋养层细胞侵润的重要通路的影响，并通过芯片筛查LC3B和Beclin1敲低和过表达对滋养层细胞中基因表达的影响。运用分子生物学和动物实验方法确认LC3B和Beclin1调控滋养层细胞侵袭的上下游分子，最终阐明LC3B和Beclin1调控滋养层细胞侵袭的分子机制。我们的研究将有阐明LC3B和Beclin1的功能，拓展我们对妊娠相关疾病发生发展的认识，为妊娠相关疾病的预防及治疗提供理论依据。

中文关键词： 不明原因复发性流产；滋养层细胞；自噬相关基因；细胞侵润；基因调控

英文摘要： Unexplained recurrent miscarriage (RM) is a common complication of human pregnancy. Recently, study found that the incidence of the disease is associated with impaired trophoblast proliferation and invasion. Our previous studies also found that autophagy-related genes, LC3B and Beclin1 expression is increased significantly in villi tissue of RM patients compared with healthy controls, and further demonstrated these proteins could regulate the invasion ability of trophoblasts in vitro. On the basis, this project aims to study the molecular mechanisms of LC3B and Beclin1 regulation of trophoblast invasion. First, we detected the signaling pathway involved in invasion ability of trophoblast by knockdown or overexpression of LC3B and Beclin1, and screened gene expression of the trophoblast by using mRNA microarray. Using molecular biology methods and animal experiments, we confirmed on the up- and down-stream molecules of LC3B and Beclin1 regulated trophoblast invasion. Finally, these results will clarify the molecular mechanisms of LC3B and Beclin1 regulation trophoblast invasion. Our research will help discover and understand the biological function of LC3B and Beclin1, expanding our understanding of the development of unexplained recurrent spontaneous abortion disease, and provide a new theoretical basis for treatment of unexplained recurrent miscarriages disease.

英文关键词： unexplained recurrent miscarriage;trophoblast;autophagy-related gene;cell invasion;gene regulation