芳香烃受体在耳蜗非感觉细胞中表达并调控毛细胞存活

文献信息

中文摘要

背景： 毛细胞是听觉的感觉细胞，其损伤或丢失由耳毒性药物或声创伤引起，并导致永久性听力损失，因为成年耳蜗缺乏再生能力。因此，识别调控毛细胞存活的通路至关重要。方法：在此我们研究一种新通路，即耳蜗中的芳香烃受体（AhR）信号。我们首次展示了AhR在生理条件下以及暴露于新霉素或噪声后的耳蜗中的表达模式。结果：在生理条件下，AhR在螺旋神经节神经元周围的胶质细胞中强烈表达，而在Corti器中表达较低。在新霉素处理或噪声暴露后，AhR在支持细胞中的表达增加，表明对毛细胞损伤的动态响应。这种毛细胞到支持细胞的通讯部分由嘌呤能信号介导，因为ATP处理模拟了新霉素的效果，而嘌呤能拮抗剂苏拉明处理消除了AhR上调。此外，与AhR水平正常的对照相比，从Corti器中删除AhR显著增加了新霉素处理后的毛细胞丢失。结论：我们的发现确立了AhR作为支持细胞中的细胞生物传感器，在毛细胞损伤期间上调以调控毛细胞的存活。

英文摘要

Damage or loss of hair cells, the sensory cells for hearing, is caused by ototoxic drugs or acoustic trauma, and results in permanent hearing loss because the adult cochlea lacks regenerative capacity. Therefore, identifying pathways that regulate hair cell survival is critical. Here we investigate a novel pathway, aryl hydrocarbon receptor (AhR) signaling in the cochlea. We demonstrate for the first time, the expression pattern of AhR in the cochlea under physiological conditions and after exposure to neomycin or noise. Under physiological conditions, AhR was strongly expressed in glia surrounding spiral ganglion neurons with low expression in the organ of Corti. Following neomycin treatment or noise exposure, AhR expression increased in supporting cells suggesting a dynamic response to hair cell injury. This hair cell to supporting cell communication is mediated in part by purinergic signaling, since treatment with ATP mimicked the effect of neomycin, and treatment with the purinergic antagonist suramin eliminated AhR upregulation. In addition, deletion of AhR from the organ of Corti significantly increased hair cell loss after neomycin treatment compared to controls with normal AhR levels. Our findings establish AhR as a cellular biosensor in supporting cells which is upregulated during hair cell injury to regulate the survival of hair cells.