FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway.
FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway.
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FOXG1 通过激活自噬途径促进衰老的内耳毛细胞存活
DOI：
10.1080/15548627.2021.1916194
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发表时间：
2021-12
期刊：
影响因子：
13.3
通讯作者：
Kong WJ
中科院分区：
文献类型：
--
作者：
He ZH;Li M;Fang QJ;Liao FL;Zou SY;Wu X;Sun HY;Zhao XY;Hu YJ;Xu XX;Chen S;Sun Y;Chai RJ;Kong WJ
老年性耳聋是衰老对听力的累积影响。最近的研究表明，常见的线粒体基因缺失与听觉系统退行性改变引起的耳聋密切相关，并提出其中一些核因子参与了线粒体功能的调控。然而，与年龄相关的听觉系统退化有关的详细机制尚未完全阐明。在本研究中，我们发现FOXG1通过调控巨噬/自噬在听觉退行性变过程中发挥重要作用。FOXG1的抑制降低了耳蜗毛细胞的自噬活性，导致活性氧的积累和随后的细胞凋亡。近年来的临床研究发现，阿司匹林通过调节细胞自噬和线粒体功能，在预防和治疗多种疾病中发挥重要作用。在本研究中，我们发现阿司匹林增加FOXG1的表达，进一步激活自噬，减少活性氧的产生，抑制凋亡，从而促进模拟衰老的hc和hc样OC-1细胞的存活。本研究揭示了FOXG1转录因子通过自噬途径在老年性耳聋毛细胞退行性变过程中的调控作用，为老年性耳聋的分子治疗提供了新的途径。AHL：年龄相关性听力损失；baf：巴霉素A1；CD：普通删除；D-gal: D-galactose;GO：葡萄糖氧化酶；HC：毛细胞；mtDNA：线粒体DNA；说唱:雷帕霉素;ROS：活性氧；四甲基罗丹明乙酯
Presbycusis is the cumulative effect of aging on hearing. Recent studies have shown that common mitochondrial gene deletions are closely related to deafness caused by degenerative changes in the auditory system, and some of these nuclear factors are proposed to participate in the regulation of mitochondrial function. However, the detailed mechanisms involved in age-related degeneration of the auditory systems have not yet been fully elucidated. In this study, we found that FOXG1 plays an important role in the auditory degeneration process through regulation of macroautophagy/autophagy. Inhibition of FOXG1 decreased the autophagy activity and led to the accumulation of reactive oxygen species and subsequent apoptosis of cochlear hair cells. Recent clinical studies have found that aspirin plays important roles in the prevention and treatment of various diseases by regulating autophagy and mitochondria function. In this study, we found that aspirin increased the expression of FOXG1, which further activated autophagy and reduced the production of reactive oxygen species and inhibited apoptosis, and thus promoted the survival of mimetic aging HCs and HC-like OC-1 cells. This study demonstrates the regulatory function of the FOXG1 transcription factor through the autophagy pathway during hair cell degeneration in presbycusis, and it provides a new molecular approach for the treatment of age-related hearing loss. Abbreviations: AHL: age-related hearing loss; baf: bafilomycin A1; CD: common deletion; D-gal: D-galactose; GO: glucose oxidase; HC: hair cells; mtDNA: mitochondrial DNA; RAP: rapamycin; ROS: reactive oxygen species; TMRE: tetramethylrhodamine, ethyl ester
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影响因子：
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