脂氧素A4调控ILK信号通路抑制EMT抗胚胎着床的机制研究

项目名称： 脂氧素A4调控ILK信号通路抑制EMT抗胚胎着床的机制研究

项目编号： No.81471493

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： 许张晔

作者单位： 温州医科大学

项目金额： 70万元

中文摘要： 新近研究表明上皮-间质转化（EMT)与胚胎着床密切相关；整合素连接激酶(ILK)在EMT过程中扮演重要角色。然而，目前其机制尚不十分清楚。我们前期工作发现炎症的刹车信号- - 脂氧素A4 (LXA4)具有抗胚胎着床功能，抑制ILK 活化和抑制子宫内膜和滋养细胞EMT 等，因此，推测LXA4 可能通过调控ILK 信号通路抑制EMT抗胚胎着床。以动物模型观察LXA4对胚胎着床的影响及其与ILK，EMT表达变化的关系；体外实验观察LXA4 对滋养层细胞EMT 的影响和该过程与ILK 及下游分子表达的关系；RNA 干扰实验在细胞及动物模型上观察ILK、脂氧素受体（FPR2）的缺失表达与LXA4 抗胚胎着床的关系，阐明LXA4 的抗胚胎着床作用是否为ILK 和FPR2 依赖，旨在进一步揭示LXA4 抗胚胎着床的分子机制，为开发新的避孕药物提供理论基础。

中文关键词： 胚胎着床；脂氧素A4；上皮-间质转化；整合素连接激酶

英文摘要： Recent studies show that EMT has a close relationship with embryo implantation, and ILK play an important role in EMT. However, the underlying mechanisms are still unclear. Our previous studies showed that LXA4, a stop signal of inflammation, had an inhibitory effect on embryo implantation, and could regulate ILK and inhibit EMT. Our studies will prove the effect of LXA4 on EMT, and embryo implantation via ILK pathway. In vivo experiments, we investigated the effect of LXA4 on the embryo implantation and the correlation with ILK expression. In vitro experiments, we investigated the effect of LXA4 on EMT, and the expressions of ILK and downstream molecules, and the correlation between them. In RNA interference experiments, we investigated the inhibitory effect of LXA4 on embryo implantation by silencing ILK or FPR2 to illustrate whether the anti-embryo implantation effect of LXA4 was ILK or FPR2-dependent. The aim is to illustrate the mechanisms of anti-embryo implantation effect of LXA4 and provides the theoretical foundation for new contraceptives.

英文关键词： Implantation;Lipoxin A4（LXA4）;Epithelial-mesenchymal transition（EMT）;Integrin-linked kinase（ILK）