转录组学揭示G3BP1-SG轴参与年龄相关性听力损失中的耳蜗毛细胞焦亡
Transcriptomics Implicates the G3BP1-SG Axis in Cochlear Hair-Cell Pyroptosis During Age-Related Hearing Loss.
文献信息
| PMID | 42860378 |
|---|---|
| 原文 | 在 PubMed 查看原文 ↗ |
| 发表日期 | 2026 |
| 作者 | Chen Li |
| 作者单位 | Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. |
| 期刊 | Journal of cellular and molecular medicine |
| SCI 分区 | Q2 |
| IF | 4.8 |
| 研究类型 | 基础研究 · 基础／转化 |
| 所属专科 | 耳科 |
中文摘要
背景： 年龄相关性听力损失（ARHL）是听觉系统的退行性改变，但其潜在机制仍不清楚。
方法： 在本研究中，我们使用RNA测序技术分析了ARHL易感的C57BL/6J（C57）小鼠和相对抵抗的CBA/CaJ（CBA）小鼠耳蜗组织中mRNA的表达谱。我们发现，在ARHL小鼠的耳蜗组织中，与应激颗粒（SGs）相关的mRNA显著增加。结合目前关于耳蜗毛细胞焦亡的研究，我们在体外构建了House Ear Institute-Organ of Corti 1（HEI-OC1）的衰老模型，发现SG表达上调，且焦亡相关蛋白的表达呈现协同上调。此外，涉及G3BP1敲低和过表达的功能研究表明，应激颗粒通过负向调控HEI-OC1细胞中的焦亡发挥保护作用。
结果： 总之，本研究结果表明，随着衰老，SG形成增加，焦亡相关标志物的激活增强。G3BP1的功能障碍进一步加剧了这些焦亡标志物，支持SG稳态在应激条件下抑制焦亡激活中的保护作用。
结论： 初步验证提示，SG-焦亡轴可能是调控耳蜗毛细胞焦亡的潜在靶点。
英文摘要
Age-related hearing loss (ARHL) is a degenerative change in the auditory system, but its underlying mechanism remains unclear. In this study, using RNA sequencing technology, we analysed the expression profiles of mRNAs in the cochlear tissues of ARHL-susceptible C57BL/6J (C57) mice and relatively resistant CBA/CaJ (CBA) mice. We found that the mRNA related to stress granules (SGs) was significantly increased in the cochlear tissues of ARHL mice. Combined with current research on the pyroptosis of cochlear hair cells, we constructed an aging model of House Ear Institute-Organ of Corti 1 (HEI-OC1) in vitro and found that the expression of SG was upregulated and the expression of pyroptosis-related proteins showed a synergistic upregulation. Furthermore, functional studies involving both G3BP1 knockdown and overexpression suggested that stress granules exert a protective effect by negatively regulating pyroptosis in HEI-OC1 cells. In summary, the results of this study indicate that with aging, the formation of SG increases and the activation of pyroptosis-related markers is enhanced. The dysfunction of G3BP1 further exacerbates these pyroptosis markers, supporting the protective role of SG homeostasis in inhibiting pyroptosis activation under stress conditions. Preliminary verification suggests that the SG-pyroptosis axis may be a potential target for regulating the pyroptosis of cochlear hair cells.