Su Zhongwu, Xiong Hao, Liu Yi, Pang Jiaqi, Lin Hanqing, Zhang Weijian, Zheng Yiqing
Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
PeerJ. 2020 Aug 19;8:e9737. doi: 10.7717/peerj.9737. eCollection 2020.
In our aging society, age-related hearing loss (AHL) is the most common sensory disorder in old people. Much progress has been made in understanding the pathological process of AHL over the past few decades. However, the mechanism of cochlear degeneration during aging is still not fully understood.
Next generation sequencing technique was used to sequence the whole transcriptome of the cochlea of C57BL/6 mice, a mouse model of AHL. Differentially expressed genes (DEGs) were identified using the Cuffdiff software. GO and KEGG pathway enrichment analyses of the DEGs were implemented by using the GOseq R package and KOBAS software, respectively.
A total of 731 genes (379 up- and 352 down-regulated) were revealed to be differentially expressed in the cochlea of aged mice compared to the young. Many genes associated with aging, apoptosis, necroptosis and particularly, inflammation were identified as being significantly modulated in the aged cochlea. GO and KEGG analyses of the upregulated DEGs revealed that the most enriched terms were associated with immune responses and inflammatory pathways, whereas many of the downregulated genes are involved in ion channel function and neuronal signaling. Real-time qPCR showed that HO treatment significantly induced the expression of multiple inflammation and necroptosis-related genes in HEI-OC1 cells.
Using next generation sequencing, our transcriptomic analysis revealed the differences of gene expression pattern with age in the cochlea of C57BL/6 mice. Our study also revealed multiple immune and inflammatory transcriptomic changes during cochlear aging and provides new insights into the molecular mechanisms underlying cochlear inflammation in AHL.
在我们这个老龄化社会中，年龄相关性听力损失（AHL）是老年人中最常见的感觉障碍。在过去几十年里，人们对AHL的病理过程已有很多了解。然而，衰老过程中耳蜗退化的机制仍未完全明了。
采用下一代测序技术对AHL小鼠模型C57BL/6小鼠的耳蜗全转录组进行测序。使用Cuffdiff软件鉴定差异表达基因（DEG）。分别使用GOseq R包和KOBAS软件对DEG进行GO和KEGG通路富集分析。
与年轻小鼠相比，老年小鼠耳蜗中共有731个基因差异表达（379个上调，352个下调）。许多与衰老、凋亡、坏死性凋亡尤其是炎症相关的基因在老年耳蜗中被鉴定为受到显著调控。对上调的DEG进行GO和KEGG分析发现，最富集的条目与免疫反应和炎症通路相关，而许多下调基因参与离子通道功能和神经元信号传导。实时定量PCR显示，HO处理显著诱导了HEI-OC1细胞中多个炎症和坏死性凋亡相关基因的表达。
通过下一代测序，我们的转录组分析揭示了C57BL/6小鼠耳蜗中基因表达模式随年龄的差异。我们的研究还揭示了耳蜗衰老过程中的多种免疫和炎症转录组变化，并为AHL中耳蜗炎症的分子机制提供了新见解。
