The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways
The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways
复制标题
核转录因子FoxG1通过调节自噬途径影响模拟衰老毛细胞对炎症的敏感性
DOI：
10.1016/j.redox.2019.101364
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发表时间：
2020-01-01
期刊：
影响因子：
11.4
通讯作者：
Kong, Wei-jia
中科院分区：
文献类型：
--
作者：
He, Zu-hong;Zou, Sheng-yu;Kong, Wei-jia
炎症是一种自我防御反应，以保护个体免受感染和组织损伤，但过度或持续的炎症可能对细胞存活产生不利影响。随着年龄的增长，许多人变得特别容易受到慢性炎症引起的感音神经性听力损失的影响，但老年人听力损失风险增加背后的内在分子机制仍不清楚。FoxG 1（叉头框转录因子G1）是一种关键的转录因子，通过调节线粒体功能在毛细胞存活中起重要作用，但FoxG 1的功能在衰老和炎症条件下如何变化尚不清楚。在本研究中，我们首次发现在低浓度脂多糖（LPS）诱导的炎症模型中，FoxG 1表达和自噬水平均逐渐增加，而在高浓度LPS处理后，FoxG 1表达和自噬水平均随着LPS浓度的增加而降低。然后，我们使用siRNA下调毛细胞样OC-1细胞中Foxg 1的表达，发现LPS损伤后细胞死亡和凋亡显著增加。此外，我们使用D-半乳糖（D-gal）建立体外培养毛细胞样OC-1细胞和耳蜗外植体的衰老模型，发现D-gal和LPS共同处理后Foxg 1的表达和自噬水平均降低。最后，我们在老年炎症条件下敲低Foxg 1的表达，发现死亡和凋亡细胞的数量增加。这些结果表明，FoxG 1通过调节自噬途径影响模拟衰老毛细胞对炎症的敏感性。
Inflammation is a self-defense response to protect individuals from infection and tissue damage, but excessive or persistent inflammation can have adverse effects on cell survival. Many individuals become especially susceptible to chronic-inflammation-induced sensorineural hearing loss as they age, but the intrinsic molecular mechanism behind aging individuals' increased risk of hearing loss remains unclear. FoxG1 (forkhead box transcription factor G1) is a key transcription factor that plays important roles in hair cell survival through the regulation of mitochondrial function, but how the function of FoxG1 changes during aging and under inflammatory conditions is unknown. In this study, we first found that FoxG1 expression and autophagy both increased gradually in the low concentration lipopolysaccharide (LPS)-induced inflammation model, while after high concentration of LPS treatment both FoxG1 expression and autophagy levels decreased as the concentration of LPS increased. We then used siRNA to downregulate Foxg1 expression in hair cell-like OC-1 cells and found that cell death and apoptosis were significantly increased after LPS injury. Furthermore, we used D-galactose (D-gal) to create an aging model with hair cell-like OC-1 cells and cochlear explant cultures in vitro and found that the expression of Foxg1 and the level of autophagy were both decreased after D-gal and LPS co-treatment. Lastly, we knocked down the expression of Foxg1 under aged inflammation conditions and found increased numbers of dead and apoptotic cells. Together these results suggest that FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.