实验性自身免疫性脑脊髓炎的 miRNA 表达谱揭示了新的潜在疾病生物标志物。
The miRNA Expression Profile of Experimental Autoimmune Encephalomyelitis Reveals Novel Potential Disease Biomarkers.
机构信息
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Institute of Genomic Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
出版信息
Int J Mol Sci. 2018 Dec 11;19(12):3990. doi: 10.3390/ijms19123990.
Multiple sclerosis (MS) is a debilitating autoimmune disease affecting over 2.3 million people worldwide, and it is characterized by inflammation and demyelination of nerve cells. The currently available biomarkers for the diagnosis and management of MS have inherent limitations, therefore, additional new biomarkers are needed. We studied the microRNA (miRNA) profile of splenocytes of mice having experimental autoimmune encephalomyelitis (EAE), a model of human MS. A miRNA-microarray analysis revealed increased expression of nine miRNAs (let-7e, miR-23b, miR-31, miR-99b, miR-125a, miR-146b, miR-155, miR-193b, and miR-221) following EAE development. Interestingly, serum levels of miR-99b, miR-125a, and miR-146b were significantly higher in EAE mice compared to normal mice. Bioinformatics analysis revealed the experimentally validated as well as predicted gene targets of specific miRNAs that are important for disease progression in MS. Specifically, we observed inverse correlation in the levels of miR-99b versus , and between miR-125a versus and . Our results suggest that above-mentioned miRNAs may play a crucial role in the pathogenesis of MS, and that miR-99b, miR-125a, and miR-146b in particular may serve as useful biomarkers for disease activity.
多发性硬化症（MS）是一种使人衰弱的自身免疫性疾病，影响着全球超过 230 万人，其特征是神经细胞的炎症和脱髓鞘。目前用于 MS 诊断和管理的生物标志物存在固有局限性，因此需要额外的新生物标志物。我们研究了实验性自身免疫性脑脊髓炎（EAE）小鼠脾细胞的 microRNA（miRNA）谱，EAE 是人类 MS 的模型。miRNA 微阵列分析显示，在 EAE 发展后，有 9 种 miRNA（let-7e、miR-23b、miR-31、miR-99b、miR-125a、miR-146b、miR-155、miR-193b 和 miR-221）的表达增加。有趣的是，与正常小鼠相比，EAE 小鼠的血清 miR-99b、miR-125a 和 miR-146b 水平明显更高。生物信息学分析揭示了特定 miRNA 的实验验证以及预测基因靶标，这些靶标对 MS 疾病进展很重要。具体来说，我们观察到 miR-99b 与 之间的水平呈负相关，miR-125a 与 之间呈负相关。我们的结果表明，上述 miRNA 可能在 MS 的发病机制中发挥关键作用，特别是 miR-99b、miR-125a 和 miR-146b 可能作为疾病活动的有用生物标志物。
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