Department of Otolaryngology, The First People’s Hospital of Changzhou, Jiangsu 213003, China.
Department of Cardiothoracic Surgery, The First People’s Hospital of Changzhou, Jiangsu 213003, China.
Aging (Albany NY). 2024 Oct 30;16(20):13132-13144. doi: 10.18632/aging.206138.
Age-related hearing loss (AHL) is a prevalent and multifaceted condition that significantly impacts a substantial portion of the aging population. Oxysterol Binding Protein-like 2 (OSBPL2) has been identified as a causal gene for hearing loss. However, its role in AHL is still unclear. In this study, we investigated the effect of OSBPL2 on the survival of cochlea hair cells. To simulate AHL , hair cell-like inner ear cells (HEI-OC1) were exposed to HO treatment. OSBPL2 expression was significantly increased in HEI-OC1 cells after HO treatment. OSBPL2 knockdown augmented cell death and apoptosis in HO-induced HEI-OC1 cells. Besides, HO treatment also led to the inactivation of the AKT and FOXG1 signaling pathways in HEI-OC1 cells. Mechanistically, OSBPL2 silencing reinforced the inactivation of the FOXG1 signaling pathway in HO-treated HEI-OC1 cells by inhibiting the AKT signaling pathway. Under HO treatment, AKT inhibition by MK2206 augmented the apoptosis of HEI-OC1 cells; on the contrary, AKT activation by SC79 treatment partially rescued the apoptosis of OSBPL2-knockdown HEI-OC1 cells. In addition, FOXG1 silencing significantly reversed the effects of AKT activation on OSBPL2-knockdown HEI-OC1 cells. Moreover, OSBPL2 expression and the activation status of the AKT/FOXG1 signaling pathway were confirmed in the cochleae of young and old C57BL/6 mice. In conclusion, our study provides evidence that OSBPL2 inhibition sensitizes HEI-OC1 cells to HO-induced apoptosis via inactivation of the AKT/FOXG1 signaling pathway, suggesting that OSBPL2 acts as an important regulator in AHL.
年龄相关性听力损失（AHL）是一种普遍存在且多方面的疾病，严重影响了相当一部分老年人群体。氧化固醇结合蛋白样 2（OSBPL2）已被确定为听力损失的一个致病基因。然而，其在 AHL 中的作用尚不清楚。在这项研究中，我们研究了 OSBPL2 对耳蜗毛细胞存活的影响。为了模拟 AHL，将内耳毛细胞样细胞（HEI-OC1）暴露于 HO 处理。HO 处理后，HEI-OC1 细胞中的 OSBPL2 表达显著增加。OSBPL2 敲低增强了 HO 诱导的 HEI-OC1 细胞中的细胞死亡和凋亡。此外，HO 处理还导致 HEI-OC1 细胞中 AKT 和 FOXG1 信号通路失活。在机制上，OSBPL2 沉默通过抑制 AKT 信号通路增强了 HO 处理的 HEI-OC1 细胞中 FOXG1 信号通路的失活。在 HO 处理下，MK2206 抑制 AKT 增强了 HEI-OC1 细胞的凋亡；相反，SC79 处理激活 AKT 部分挽救了 OSBPL2 敲低的 HEI-OC1 细胞的凋亡。此外，FOXG1 沉默显著逆转了 AKT 激活对 OSBPL2 敲低的 HEI-OC1 细胞的影响。此外，在年轻和老年 C57BL/6 小鼠的耳蜗中证实了 OSBPL2 表达和 AKT/FOXG1 信号通路的激活状态。总之，我们的研究提供了证据表明，OSBPL2 抑制通过失活 AKT/FOXG1 信号通路使 HEI-OC1 细胞对 HO 诱导的凋亡敏感，表明 OSBPL2 是 AHL 中的一个重要调节因子。
