Coordinated messenger RNA/microRNA changes in fibroblasts of patients with major depression.

Coordinated messenger RNA/microRNA changes in fibroblasts of patients with major depression.
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DOI:
10.1016/j.biopsych.2014.05.015
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发表时间:
2015-02-01
影响因子:
10.6
通讯作者:
Mirnics, Karoly
Mirnics, Karoly
中科院分区:
医学1区
文献类型:
--
作者:
Garbett, Krassimira A.;Vereczkei, Andrea;Kalman, Sara;Brown, Jacquelyn A.;Taylor, Warren D.;Faludi, Gabor;Korade, Zeljka;Shelton, Richard C.;Mirnics, Karoly

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在过去的半个世纪里,主要精神疾病的外周生物标记物一直是一个难以捉摸的目标。真皮成纤维细胞是研究情感性精神障碍患者分子过程的一种简单、相关且未得到充分利用的模型,因为它们与神经元组织在信号转导方面有相当大的相似性。采用基因芯片技术检测16对抑郁症患者和32例正常对照真皮成纤维细胞的全基因组m RNA表达。此外,还同时对>1000种miRNA进行了基于定量聚合酶链式反应的评估。最后,为了检验mRNA-miRNA表达变化之间的关系,对两个数据集进行了相互关联。我们的数据显示,与对照组相比,MDD成纤维细胞在多个分子途径上表现出强烈的mRNA基因表达模式的变化,包括细胞间通讯、先天/获得性免疫和细胞增殖。此外,同一患者的成纤维细胞显示出一组不同的38个miRNAs的表达变化,这些miRNAs可能针对许多差异表达的mRNAs。MiRNA-mRNA的表达变化似乎在功能上是相关的,因为大多数miRNA和mRNA的变化方向相反。我们的数据表明,联合miRNA-mRNA评估可以为疾病过程提供信息,对真皮成纤维细胞的分析可能导致发现有希望的MDD外周生物标记物,这些标记物可能被用于辅助诊断并允许对紊乱的分子通路进行机械测试。
Peripheral biomarkers for major psychiatric disorders have been an elusive target for the last half a century. Dermal fibroblasts are a simple, relevant, and much underutilized model for studying molecular processes of patients with affective disorders as they share considerable similarity of signal transduction with neuronal tissue. Cultured dermal fibroblast samples from patients with Major Depressive Disorder (MDD) and matched controls (CNTR) (n=16 pairs, 32 samples) were assayed for genome wide mRNA expression using microarrays. In addition, a simultaneous qPCR-based assessment of >1,000 miRNA species was performed. Finally, to test the relationship between the mRNA-miRNA expression changes, the two datasets were correlated with each other. Our data revealed that MDD fibroblasts, when compared to matched controls, showed a strong mRNA gene expression pattern change in multiple molecular pathways, including cell-to-cell communication, innate/adaptive immunity and cell proliferation. Furthermore, the same patient fibroblasts showed altered expression of a distinct panel of 38 miRNAs, which putatively targeted many of the differentially expressed mRNAs. The miRNA-mRNA expression changes appeared to be functionally connected, as the majority of the miRNA and mRNA changes were in the opposite direction. Our data suggest that a combined miRNA-mRNA assessments are informative about the disease process, and that analyses of dermal fibroblasts might lead to the discovery of promising peripheral biomarkers of MDD, which could be potentially used to aid the diagnosis and allow mechanistic testing of disturbed molecular pathways.
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