The changes of miRNA expression in rat hippocampus following chronic lead exposure
The changes of miRNA expression in rat hippocampus following chronic lead exposure
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慢性铅暴露后大鼠海马miRNA表达的变化
DOI：
10.1016/j.toxlet.2014.06.002
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发表时间：
2014-08-17
影响因子：
3.5
通讯作者：
Luo, Wenjing
中科院分区：
文献类型：
--
作者：
An, Jun;Cai, Tongjian;Luo, Wenjing
已经发现miRNA有助于正常的脑功能、神经系统疾病以及由外部试剂诱导的神经毒性。然而，它们是否参与铅诱导的神经毒性仍不清楚。为证实铅对神经系统的毒性作用，建立了铅慢性神经毒性大鼠模型。采用微阵列技术和qRT-PCR技术检测海马组织中miRNA表达的变化。利用3个生物信息学数据库对这些miRNA的相关靶基因进行分析，并通过qRT-PCR和Western blot进行验证。在本研究中，铅暴露导致7种miRNAs的表达变化：miR-204、miR-211、miR-448、miR-449 a、miR-34 b和miR-34 c显著上调，而miR-494显著下调。生物信息学分析结果表明，6个上调的miRNAs靶基因与神经损伤和神经变性、轴突和突触功能、神经发育和再生相关。相应地，Bcl-2、Itpr 1和Map 2k 1三个靶基因的成熟mRNA和蛋白表达水平均受到抑制，验证了生物信息学分析的结果。总之，我们的研究结果表明，在大鼠海马慢性铅暴露后，几种与神经生理通路和神经退行性疾病相关的miRNA的表达发生了变化。这些miRNAs可能在铅诱导的神经毒性中发挥重要作用。(C)由Elsevier爱尔兰Ltd.出版
miRNAs have been found to contribute to normal brain functions, nervous system diseases, as well as neurotoxicities induced by external agents. However, whether they are involved in lead-induced neurotoxicities is still not clear. To identify that, a lead-induced chronic neurotoxicity model of rats was built. Both miRNA microarray analysis and qRT-PCR were performed to determine the change of miRNA expression in hippocampus. Then 3 bioinformatics databases were used to analyze the relative target genes of these miRNA, which were further confirmed by qRT-PCR and Western blot. In the present study, lead exposure resulted in the changed expression of 7 miRNAs: miR-204, miR-211, miR-448, miR-449a, miR-34b, and miR-34c were greatly up-regulated while miR-494 was greatly down-regulated. Bioinformatics analysis results showed that the target genes of 6 up-regulated miRNAs were related to neural injury and neurodegeration, axon and synapse function, neural development and regeneration. Correspondingly, the expression levels of mature mRNAs and proteins of three target genes (Bcl-2, Itpr1, and Map2k1) were greatly repressed, verifying the results of bioinformatics analysis. Taken together, our results showed that the expression of several miRNAs reported to be associated with neurophysiological pathways and neurodegenerative diseases changed in rat hippocampus following chronic lead exposure. These miRNAs may play important roles in lead-induced neurotoxicity. (C) 2014 Published by Elsevier Ireland Ltd.