Spontaneous regeneration mechanism of inner ear outer hair cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06466
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• 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)
• Co-Investigator(Kenkyū-buntansha): 和田 健太 東京農業大学, 生物産業学部, 教授 (20508113)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 難聴 / 外有毛細胞 / 再生 / マウスモデル

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.

Free Research Field

実験動物学

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。