An experimental study of master transcription factors that regulate gene expressions in cochleae with acute sensorineural hearing loss

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09756
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Okayama University
• Principal Investigator: Takahara Junko 岡山大学, 総合技術部, 技術専門職員 (80448224)
• Co-Investigator(Kenkyū-buntansha): 前田 幸英 岡山大学, 大学病院, 講師 (00423327)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 急性感音難聴 / 蝸牛 / 転写因子 / 遺伝子発現解析 / RNA-seq / DNAマイクロアレイ

Outline of Final Research Achievements

Acute noise trauma is a major form of acute sensorineural hearing loss. It was previously shown that several dozens of inflammation and immunity related genes are up- and downregulated in cochleae at 12 hours post-noise trauma in mice. In this study it was shown that an immunity-regulating transcription factor, Atf3 （Activatinng Transcription　Factor3）is upregulated in mice cochleae with more than 8-fold change in expression levels in 3 and 12 hours post noise trauma. Immunohistochemical experiments showed that Atf3 is expressed in the sensory epithelium of organ of Corti at these time points. An other immunity-regulating transcription factor Stat4 (Signal transducer and activator of transcription 4) showed a tendency of downregulation in cochleae at 12 hours post-noise trauma. Gene expression analysis by RNA-seq, DNA microarray, and realtime RT-PCR showed that other transcription factors, Dbp, Helt, Maff, Nr1d1 expressions are upregulated in cochleae at 3 hours post-noise trauma.

Free Research Field

耳鼻咽喉科学

Academic Significance and Societal Importance of the Research Achievements

急性感音難聴は耳鼻咽喉科の臨床では比較的頻繁にみられ、かつ難治性の病態である。音響外傷により急性感音難聴を呈するマウスの蝸牛では、発症早期に炎症・免疫に関連する遺伝子群が多数変動するが、当研究で検討したAtf3等はそれらの遺伝子発現をコントロールする転写因子であると考えられる。これらの転写因子は、急性感音難聴の発症リスク予測法、治療法やその効果の予測法の開発において、有力な解析ターゲットとなる。