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タイトル: | Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea |
著者: | Liu, L Chen, Y Qi, J Zhang, Y He, Y Ni, W Li, W Zhang, S Sun, S Taketo, M M Wang, L Chai, R Li, H |
著者名の別形: | 武藤, 誠 |
キーワード: | Immunology Cell Biology Cancer Research Cellular and Molecular Neuroscience |
発行日: | 10-Mar-2016 |
出版者: | Springer Nature |
誌名: | Cell Death and Disease |
巻: | 7 |
論文番号: | e2136 |
抄録: | Recent studies have reported the role of Wnt/β-catenin signaling in hair cell (HC) development, regeneration, and differentiation in the mouse cochlea; however, the role of Wnt/β-catenin signaling in HC protection remains unknown. In this study, we took advantage of transgenic mice to specifically knockout or overactivate the canonical Wnt signaling mediator β-catenin in HCs, which allowed us to investigate the role of Wnt/β-catenin signaling in protecting HCs against neomycin-induced damage. We first showed that loss of β-catenin in HCs made them more vulnerable to neomycin-induced injury, while constitutive activation of β-catenin in HCs reduced HC loss both in vivo and in vitro. We then showed that loss of β-catenin in HCs increased caspase-mediated apoptosis induced by neomycin injury, while β-catenin overexpression inhibited caspase-mediated apoptosis. Finally, we demonstrated that loss of β-catenin in HCs led to increased expression of forkhead box O3 transcription factor (Foxo3) and Bim along with decreased expression of antioxidant enzymes; thus, there were increased levels of reactive oxygen species (ROS) after neomycin treatment that might be responsible for the increased aminoglycoside sensitivity of HCs. In contrast, β-catenin overexpression reduced Foxo3 and Bim expression and ROS levels, suggesting that β-catenin is protective against neomycin-induced HC loss. Our findings demonstrate that Wnt/β-catenin signaling has an important role in protecting HCs against neomycin-induced HC loss and thus might be a new therapeutic target for the prevention of HC death. |
著作権等: | Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0 |
URI: | http://hdl.handle.net/2433/226848 |
DOI(出版社版): | 10.1038/cddis.2016.35 |
PubMed ID: | 26962686 |
出現コレクション: | 学術雑誌掲載論文等 |
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