Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.
Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.
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DOI：
10.1371/journal.pone.0062786
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
He DZ
中科院分区：
文献类型：
--
作者：
Zhang Q;Liu H;McGee J;Walsh EJ;Soukup GA;He DZ
MicroRNA (miRNA) 是一类调节 mRNA 靶标表达的短非编码 RNA，是细胞衰老和老化的重要调节因子。我们质疑哪些 miRNA 参与了柯蒂氏器 (OC) 的年龄相关变性，柯蒂氏器是将机械刺激转换为内耳电活动的听觉感觉上皮。 OC 退化被普遍认为是年龄相关性听力损失 (ARHL) 的主要原因，ARHL 是个体随着年龄的增长而逐渐丧失听力的疾病。为了确定哪些 miRNA 参与 ARHL 的发病和进展，使用 GeneChip miRNA 微阵列比较了两种小鼠品系（C57BL/6J 和 CBA/J）OC 中 miRNA 基因的表达，并通过实时 PCR 进行了验证。我们发现，C57 和 CBA 小鼠中分别有 111 和 71 个 miRNA 表现出差异表达，并且在衰老过程中下调的 miRNA 数量大大多于上调的 miRNA。上调约 2 倍的 miRNA 包括 miR-29 家族和 miR-34 家族的成员，它们是已知的促凋亡途径的调节因子。相比之下，下调约2倍的miRNA是miR-181家族和miR-183家族的成员，已知它们分别对增殖和分化很重要。 miRNA 表达有利于细胞凋亡的转变发生得早于可检测到的听力阈值升高和毛细胞损失。我们的研究表明，miRNA 表达的变化先于形态和功能的变化，并且促凋亡 miRNA 的上调和促进增殖和分化的 miRNA 的下调都与 OC 的年龄相关变性有关。
MicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression of mRNA targets, are important regulators of cellular senescence and aging. We questioned which miRNAs are involved in age-related degeneration of the organ of Corti (OC), the auditory sensory epithelium that transduces mechanical stimuli to electrical activity in the inner ear. Degeneration of the OC is generally accepted as the main cause of age-related hearing loss (ARHL), a progressive loss of hearing in individuals as they grow older. To determine which miRNAs are involved in the onset and progression of ARHL, miRNA gene expression in the OC of two mouse strains, C57BL/6J and CBA/J, was compared at three different ages using GeneChip miRNA microarray and was validated by real-time PCR. We showed that 111 and 71 miRNAs exhibited differential expression in the C57 and CBA mice, respectively, and that downregulated miRNAs substantially outnumbered upregulated miRNAs during aging. miRNAs that had approximately 2-fold upregulation included members of miR-29 family and miR-34 family, which are known regulators of pro-apoptotic pathways. In contrast, miRNAs that were downregulated by about 2-fold were members of the miR-181 family and miR-183 family, which are known to be important for proliferation and differentiation, respectively. The shift of miRNA expression favoring apoptosis occurred earlier than detectable hearing threshold elevation and hair cell loss. Our study suggests that changes in miRNA expression precede morphological and functional changes, and that upregulation of pro-apoptotic miRNAs and downregulation of miRNAs promoting proliferation and differentiation are both involved in age-related degeneration of the OC.
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