海南热带海洋学院学报2025，Vol.32Issue(2)：138-148,11.DOI:10.13307/j.issn.2096-3122.2025.02.15
应用腺病毒载体技术诱导幼鼠耳蜗毛细胞的再生
Application of Adenoviral Vector Technology to Induce Hair Cell Regeneration in the Cochlea of Neonatal Mice
摘要
Abstract
By altering the activity of Notch and Wnt signaling pathways through adenovirus-mediated gene transfer,the hair cell regeneration in the cochlea of mice after injury was promoted.First,an adenovirus(AD)overexpressing β-catenin was constructed to increase the activity of the Wnt signaling pathway,and another AD interfering with NICD was developed to reduce the activity of the Notch signaling pathway.These adenoviruses were then introduced into ex-plants of the cochleae of neonatal mice that had been damaged by gentamicin,and the regeneration of hair cells was mea-sured.Real-time quantitative PCR after adenoviral transfection demonstrated that high-titer(1×108 PFU·mL-1)adenovirus primarily infected supporting cells and some hair cells.When cochlear explants were treated with adenoviral transfection,the mitotic regeneration increased following the enhancement of Wnt signaling pathway activity mediated by β-catenin-AD,and the direct transdifferentiation from supporting cells to hair cells increased following the reduction of Notch signaling pathway activity mediated by NICD-RNAi-AD.The experimental results show that the alteration of Wnt and Notch signal-ing pathway activities through adenoviral transfection enables the regeneration of hair cells in the cochlea of young mice af-ter damage.This gene therapy and technology using adenoviral vectors to modulate Wnt and Notch signaling pathways for the treatment of hearing loss is feasible.关键词
腺病毒转染技术/抑制Notch通路/激活Wnt通路/耳蜗损伤/毛细胞再生/小鼠Key words
adenoviral transfection technology/inhibition of Notch pathway/activation of Wnt pathway/cochlear dam-age/hair cell regeneration/mice分类
医药卫生引用本文复制引用
张信文,翁梦露,赵汝霞,牛巧花,杨思远,曾少举..应用腺病毒载体技术诱导幼鼠耳蜗毛细胞的再生[J].海南热带海洋学院学报,2025,32(2):138-148,11.基金项目
国家自然科学基金项目(31860269) （31860269）
海南省自然科学基金项目(319QN238) （319QN238）
