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Wnt signaling activation for regeneration of inner ear hair cell

Wnt信号激活促进内耳毛细胞再生

基本信息

批准号：
17591787
负责人：
TAMURA Yoshihiro
金额：
$ 2.24万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591787/
关键词：
Wnt signaling senorineural hearing loss beta-catenin stabilized mouse GSK-3β conditional knockout Cre-loxP system hair cell 有毛臍傍 in vivo コンディショナル・ノック

项目摘要

1.Knockout of GSK-36Wnt signaling is the important signal transduction pathway for cell proliferation. Beta-catenin stabilized mouse was used as experimental animal. Using adenovirus vector and Cre-loxP system in the culture preparation of organ of Corti at various conditions, we tried to knock out GSK-36; a inhibiting factor of Wnt signaling.2.Pharmacological inhibition of GSK-36In the culture preparation of organ of Corti, GSK-36 was blocked by several drugs, such as Kenpaullone Indirubin-3'-monoxime. GSK-3 Inhibitor II, BIO and so on. In some specimens, hair cells seemed to be proliferated.3.In vivo experiments on activation of Wnt signalingFollowing in vitro experiments, in vivo regeneration of inner ear hair cells has been tried by activating of Wnt signal through round window for future clinical application. Two types of administration devices, continuous infusion pump and biodegradable hydrogel, have been used. However, proliferation and regeneration of inner ear hair cells have not been observed yet.

1.GSK-36Wnt信号的敲除是细胞增殖的重要信号转导途径。实验动物为β-连环蛋白稳定化小鼠。利用腺病毒载体和Cre-loxP系统在不同条件下对Wnt信号的抑制因子GSK-36进行敲除。2.GSK-36的药理抑制在Corti器官的培养制剂中，GSK-36可被几种药物阻断。GSK-3抑制剂II、BIO等。Wnt信号激活的体内实验继体外实验之后，我们尝试了通过圆窗激活Wnt信号的方法实现内耳毛细胞的体内再生，为以后的临床应用奠定了基础。使用了两种给药装置：连续输液泵和生物可降解水凝胶。然而，尚未观察到内耳毛细胞的增殖和再生。