Hippo/YAP signaling pathway protects against neomycin-induced hair cell damage in the mouse cochlea

作者：Maohua Wang, Ying Dong, Song Gao, Zhenhua Zhong, Cheng Cheng, Ruiying Qiang, Yuhua Zhang, Xinyi Shi, Xiaoyun Qian, Xia Gao, Bing Guan, Chenjie Yu, Youjun Yu, Renjie Chai · 发表于：Cellular and Molecular Life Sciences · 年份：2022 · DOI：10.1007/s00018-021-04029-9 · 被引用次数：58 · 研究领域：Hippo pathway signaling and YAP/TAZ、Wnt/β-catenin signaling in development and cancer、Cancer-related molecular mechanisms research

The Hippo/Yes-associated protein (YAP) signaling pathway has been shown to be able to maintain organ size and homeostasis by regulating cell proliferation, differentiation, and apoptosis. The abuse of aminoglycosides is one of the main causes of sensorineural hearing loss (SSNHL). However, the role of the Hippo/YAP signaling pathway in cochlear hair cell (HC) damage protection in the auditory field is still unclear. In this study, we used the YAP agonist XMU-MP-1 (XMU) and the inhibitor Verteporfin (VP) to regulate the Hippo/YAP signaling pathway in vitro. We showed that YAP overexpression reduced neomycin-induced HC loss, while downregulated YAP expression increased HC vulnerability after neomycin exposure in vitro. We next found that activation of YAP expression inhibited C-Abl-mediated cell apoptosis, which led to reduced HC loss. Many previous studies have reported that the level of reactive oxygen species (ROS) is significantly increased in cochlear HCs after neomycin exposure. In our study, we also found that YAP overexpression significantly decreased ROS accumulation, while downregulation of YAP expression increased ROS accumulation. In summary, our results demonstrate that the Hippo/YAP signaling pathway plays an important role in reducing HC injury and maintaining auditory function after aminoglycoside exposure. YAP overexpression could protect against neomycin-induced HC loss by inhibiting C-Abl-mediated cell apoptosis and decreasing ROS accumulation, suggesting tha...