Spontaneous regeneration mechanism of inner ear outer hair cells
| Project/Area Number |
20K06466
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 42040:Laboratory animal science-related
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
MATSUOKA Kunie 公益財団法人東京都医学総合研究所, 基礎医科学研究分野, 研究員 (40291158)
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| Co-Investigator(Kenkyū-buntansha) |
和田 健太 東京農業大学, 生物産業学部, 教授 (20508113)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 難聴 / 外有毛細胞 / 再生 / マウスモデル / 内耳外有毛細胞 / ダイテルス細胞 / RNA-seq |
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| Outline of Research at the Start |
「聞こえの調節」に重要な役割を担っている内耳外有毛細胞（OHC）は騒音などにより障害を受け、また加齢によっても減少する。哺乳類のOHCは一度失われると再生しないとされてきたが、我々はこれまでに開発したOHC破壊マウスを解析する過程で、OHCを急激に破壊するとOHCが自発的に再生する可能性があることを見出した。そこで、OHC破壊マウスを利用してOHC破壊後の遺伝子発現、形態、聴力の変化を詳細に観察してOHCの再生の可能性を探り、そのメカニズムを解明する。
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| Outline of Final Research Achievements |
We obtained traces of spontaneous OHC regeneration after abrupt destruction using Prestin-hDTR mice. Regeneration seemed to mimic the natural process of development. We found that Agr3 whose function in hearing was unknown, were remarkably downregulated by OHC-depletion at a neonatal stage. Immunohistochemical studies revealed that AGR3 was not expressed in OHCs but in Deiters' cells which are the supporting cells of OHCs. Our finding in this study suggested that there are close crosstalk processes between OHCs and Deiters’ cells in OHC development. In contrast, we assayed the effects of Wnt signaling inhibitor RPI-724 on OHC regeneration. We observed recovery of hearing by administration of the RPI-724 three times a week for 12 weeks to adult OHC-depleted mice. It was suggested that inhibition of Wnt/β-catenin/CBP signaling promotes regeneration of OHCs.
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| Academic Significance and Societal Importance of the Research Achievements |
内耳外有毛細胞(OHC)は鋭敏な聴覚を得るために極めて重要である。OHCは加齢・騒音・感染・アミノグリコシド系抗生剤の投与等によって損傷を受け、哺乳類では一度失われると再生しないとされてきたが、我々はOHCが急激に破壊されるとOHCの自発的な再生が誘導される可能性を見出した。現在、難聴の根本的な治療法はなく、補聴器や人工内耳の装用により聴力を補わざるを得ないが、OHCの自発的な再生のメカニズムが明らかになれば、再生を促進させるための創薬や治療法の確立に向けて極めて重要な情報を提供することとなる。
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Two Loci Contribute to Age-Related Hearing Loss Resistance in the Japanese Wild-Derived Inbred MSMMs Mice2022
Author(s)
Shumpei P. Yasuda, Yuki Miyasaka, Xuehan Hou, Yo Obara, Hiroshi Shitara, Yuta Seki, Kunie Matsuoka, Ai Takahashi, Eri Wakai, Hiroshi Hibino, Toyoyuki Takada, Toshihiko Shiroishi, Ryo Kominami and Yoshiaki Kikkawa
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Journal Title
Biomedicines
Volume: 10
Issue: 9
Pages: 2221-2221
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Two loci, ahl3 and ahl10, contribute to age-related hearing loss resistance in Japanese wild-derived inbred MSM/Ms mice2023
Author(s)
Yasuda SP, Miyasaka Y, Hou X, Obara Y, Shitara H, Seki Y, Matsuoka K, Takahashi A, Wakai E, Hibino H, Takada T, Shiroishi T, Kominami R, Kikkawa Y
Organizer
36th International Mammalian Genome Conference
Related Report
Int'l Joint Research
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