Autophagy acceleration attenuates endoplasmic stress-induced cell death in auditory cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18747
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Tohoku University (2020); Nihon University (2019)
• Principal Investigator: Kishino Akihiro 東北大学, 加齢医学研究所, 分野研究員 (80825307)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 感音難聴 / 内耳感覚細胞 / 小胞体ストレス / オートファジー / 細胞死

Outline of Final Research Achievements

Autophagy dysfunction and endoplasmic reticulum (ER) stress in auditory cells are associated with the pathogenesis of sensorineural hearing loss (SNHL). This study aimed to uncover the association between autophagy and cell death in auditory cells under ER stress. We demonstrated that the acceleration of autophagy attenuates ER stress-induced cell death in HEI-OC1 cells. This inference was based on two important findings. First, autophagy impairment by knockdown of Beclin-1 and Atg7 led to the increase C/-EBP homologous protein (CHOP) expression and promotes much more cell death. Second, autophagy induction by rapamycin, an autophagy inducer, suppressed cell death with the decrease of CHOP expression. Together, our findings revealed that autophagy upregulation serves as a prosurvival mechanism by suppressing ER stress-induced cell death in auditory cells. The present study reveals that efficient autophagy induction is a potential target for SNHL.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

感音難聴の病態生理については依然としてその病態は不明であり、有効性の明白なエビデンスを有する治療法は確立されていない。また、感音難聴の発症や予後を予期する客観性のある分子マーカーも存在しない。高度な感音難聴による患者のQOLの低下は著しく、社会的生活に大きな影響を及ぼす。また、加齢による感音難聴については高齢化社会の進行に伴い、患者数のさらなる増加が予想される。そのため、感音難聴に対する有効な新規治療法の確立の為にも病態生理の解明が求められる。
本研究における結果から、オートファジー機能の活性化は感音難聴を含む内耳疾患の病態解明や新規治療法の開発・発展応用へ貢献し得る。