Hippo-YAP信号通路对小鼠耳蜗毛细胞再生的调控作用研究

项目名称： Hippo-YAP信号通路对小鼠耳蜗毛细胞再生的调控作用研究

项目编号： No.81670928

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 俞晨杰

作者单位： 南京大学

项目金额： 25万元

中文摘要： 感觉毛细胞在听觉功能中起着重要作用，毛细胞的损伤将直接导致听力损失。研究表明，毛细胞损伤后Lgr5阳性内耳干细胞可以再生毛细胞，并且该过程受到Wnt信号调控。在多种器官中已有报导Hippo信号和Wnt信号存在相互作用；但是Hippo信号对毛细胞再生的调控机制还不清楚。本项目将研究Hippo信号对内耳干细胞的调控机制，以促进其再生有功能的毛细胞，从而重建内耳结构和功能。拟实现以下目标：一、在离体实验中研究Hippo信号对流式分选出的内耳干细胞增殖分化的调控机制；二、在离体实验中研究Hippo和Wnt信号对内耳干细胞的协同调控机制；三、在活体毛细胞新霉素损伤模型中研究Hippo信号如何调控内耳干细胞，从而促进毛细胞再生。本课题将为临床上应用内耳干细胞恢复听觉功能奠定实验基础。

中文关键词： Hippo信号；Wnt信号；Lgr5阳性内耳细胞；增殖；毛细胞再生

英文摘要： Sensory hair cells are of importance in the hearing, and the injury of the hair cells can lead to the hearing loss directly. Some studies have shown that Lgr5-positive inner ear stem cells can regenerate hair cells after hair cells damage, and this progress can be regulated by the Wnt signaling. It was reported that the Hippo signaling and the Wnt signaling can interact with each other in many organs; but the mechanism of the regeneration of hair cells regulated by the Hippo signaling remain unclear. This project would devote to study the role of the Hippo signaling in the inner ear stem cells, and further promote the regeneration of functional hair cells, and this can recover the structure and function of the inner ear. There are some aims in this project: firstly, to study the mechanism of proliferation and differentiation regulated by the Hippo signaling in the sorted inner ear stem cells; secondly, to study the mechanism of proliferation and differentiation regulated by both of the Hippo and Wnt signaling in the sorted inner ear stem cells; thirdly, to study the mechanism of regeneration of hair cells regulated by the Hippo signaling in the damaged cochlea caused by neomycin. This research would provide experimental base for recovering of the hearing function treated with inner ear stem cells clinically.

英文关键词： Hippo signaling;Wnt signaling;Lgr5-positive inner ear stem cells;proliferation;regeneration of hair cells