调控Wnt/β-catenin信号通路对耳蜗毛细胞保护作用及其机制研究

噪声、药物、感染等因素均可造成内耳毛细胞损伤和永久性听力障碍，有效的毛细胞保护及其机制研究在感音神经性聋的防治中尤为重要。Wnt/β-catenin信号通路在器官发育、细胞分化和损伤修复过程中发挥重要作用。我们既往研究提示，Wnt/β-catenin信号通路可能调控耳蜗毛细胞的存活和对耳毒性药物的敏感性。本项目在前期工作基础上，研究Wnt/β-catenin信号通路对耳蜗毛细胞的保护作用及其机制。采用β-catenin转基因敲除和高表达小鼠，结合Wnt/β-catenin信号通路的抑制剂和激动剂，下调和上调Wnt/β-catenin信号水平，研究其在小鼠活体耳聋模型和体外毛细胞损伤模型中的保护作用；采用流式细胞分选技术纯化毛细胞，应用高通量转录组测序技术，筛选及鉴定相关的差异基因及其调控网络，并对表达差异基因进行功能鉴定，揭示Wnt/β-catenin信号通路对毛细胞保护作用的分子机制。

Given that hair cells are extremely vulnerable to various kinds of ototoxic insults like noise, drugs and infections, effective protection of hair cells and investigation of the mechanism are particularly important for prevention for sensorineural hearing loss. Wnt/β-catenin signalingplays an important role in cell differentiation, cell survival, and injury recovery process in many tissues. Our preliminary experimentssuggested that Wnt/β-cateninsignaling mightregulate cell survival of cochlear hair cells. This subject aimed to explore the protective effects and its mechanism of Wnt/β-catenin signaling during hair cell damage process. Based on our preliminary results, we will explore the protective effects of Wnt/β-catenin signaling on cochlear hair cells against neomycin damage by using transgenic knockout and overexpression mice, agonist and antagonist of Wnt/β-catenin signaling respectively. Hair cell purification will be performed by flow cytometry cell sorting.High -throughput RNA sequencing (RNA-Seq) method will be applied for whole genomic analysis of hair cells to identify the relative differentially expressed genes and their function as well as their communication networks.