Adenovirus-mediated effects of Wnt and Notch signalling pathways on hair cell regeneration in mice

Menglu Weng; Ruxia Zhao; Qiaohua Niu; Yizheng Zeng; Xi Wang; Xue Gao; Zhongming Han; Jie Bing; Chao Xi; Jin Liu; Jincao Xu; Siyuan Yang; Shaoju Zeng

doi:10.1016/j.bbrc.2023.03.056

Adenovirus-mediated effects of Wnt and Notch signalling pathways on hair cell regeneration in mice

Biochem Biophys Res Commun. 2023 May 28:658:44-54. doi: 10.1016/j.bbrc.2023.03.056. Epub 2023 Mar 31.

Authors

Menglu Weng¹, Ruxia Zhao², Qiaohua Niu³, Yizheng Zeng⁴, Xi Wang⁵, Xue Gao⁶, Zhongming Han⁷, Jie Bing⁸, Chao Xi⁹, Jin Liu¹⁰, Jincao Xu¹¹, Siyuan Yang¹², Shaoju Zeng¹³

Affiliations

¹ Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, 100875, China. Electronic address: 1792268265@qq.com.
² Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, 100875, China. Electronic address: 527203007@qq.com.
³ Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, 100875, China. Electronic address: 1906266475@qq.com.
⁴ Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, 100875, China. Electronic address: 314981296@qq.com.
⁵ Department of Otorhino, Hospital of the PLA Rocket Force, Beijing, 100088, China. Electronic address: wangxi_sunshine@126.com.
⁶ Department of Otorhino, Hospital of the PLA Rocket Force, Beijing, 100088, China. Electronic address: mixueer0110@126.com.
⁷ Department of Otorhino, Hospital of the PLA Rocket Force, Beijing, 100088, China; Department of Otorhinolaryngology, Hebei YanDa Hospital, Hebei, 065201, China. Electronic address: drhanliang@163.com.
⁸ Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, 100875, China. Electronic address: bingjie@bnu.edu.cn.
⁹ Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, 100875, China. Electronic address: xichao@bnu.edu.cn.
¹⁰ Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, 100875, China. Electronic address: liujin@bnu.edu.cn.
¹¹ Department of Otorhino, Hospital of the PLA Rocket Force, Beijing, 100088, China. Electronic address: xujincao@126.com.
¹² Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, 100875, China; Hainan Vocational University of Science and Technology, Hainan, 571126, China. Electronic address: 695788942@qq.com.
¹³ Beijing Key Laboratory of Gene Resource and Molecular Development, Beijing Normal University, 100875, China. Electronic address: sjzeng@bnu.edu.cn.

PMID: 37023614
DOI: 10.1016/j.bbrc.2023.03.056

Abstract

Some genes are delivered to cochleae by adenoviruses to restore partial hearing function. This provides promising prospects for gene therapies for hearing loss from hair cell damage. To study the adenovirus (AD)-mediated effect of the Wnt and Notch signalling pathways on hair cell regeneration in the mouse cochlea, we constructed a β-catenin-adenovirus (β-catenin-AD) to increase the activity of the Wnt signalling pathway and a NICD (intracellular domain of Notch1)-RNAi-adenovirus to decrease the activity of the Notch signalling pathway (NICD-RNAi-AD). Our study indicated that approximately 40% of supporting cells in the cochleae damaged by gentamicin were infected with the adenoviruses. Following the β-catenin-AD-mediated increase in Wnt signalling pathway activity, mitotic regeneration was increased, while direct transdifferentiation was increased after the NICD-RNAi-AD-mediated decrease in Notch signalling pathway activity. The expected synergistic interaction on hair cell regeneration was not obtained after coinfection of β-catenin-AD and NICD-RNAi-AD into the damaged cochleae, which might be due to the low cotransfection efficiency to supporting cells. Our study indicated that it may be possible to develop AD mediated gene therapies for hearing loss that act by regulating the Wnt and Notch signalling pathways.

Keywords: Adenoviruses; Gentamicin damage; Hair cells; Regeneration; Signalling pathways.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae / genetics
Adenoviridae / metabolism
Animals
Hearing Loss*
Mice
Receptors, Notch / genetics
Receptors, Notch / metabolism
Wnt Signaling Pathway / physiology
beta Catenin* / genetics
beta Catenin* / metabolism

Substances

beta Catenin
Receptors, Notch