Fibroblasts from patients with major depressive disorder show distinct transcriptional response to metabolic stressors.
Fibroblasts from patients with major depressive disorder show distinct transcriptional response to metabolic stressors.
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DOI：
10.1038/tp.2015.14
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发表时间：
2015-03-10
影响因子：
6.8
通讯作者：
Mirnics K
中科院分区：
文献类型：
--
作者：
Garbett KA;Vereczkei A;Kálmán S;Wang L;Korade Ž;Shelton RC;Mirnics K
严重抑郁障碍(MDD)越来越被视为环境应激源和遗传易感性的相互作用，最近的数据表明，这种疾病不仅影响大脑，而且影响整个身体。因此，我们的目标是确定重度抑郁症患者是否对周围组织的应激反应有异常的分子反应。我们研究了两种代谢应激源--半乳糖(GAL)或降脂(RL)对16对MDD患者和匹配的健康对照(CNTR)人成纤维细胞转录组和miRNome的影响。我们的结果表明，MDD和CNTR成纤维细胞对GAL和RL的挑战都有很强的分子反应。最重要的是，很大一部分(信使RNAs)：26-33%microRNAs(MiRNAs)：81-90%)只在MDD中观察到，而在CNTR成纤维细胞中没有观察到。应用的代谢挑战揭示了mRNA和miRNA特征，确定了MDD成纤维细胞对每种应激源特征的反应。MDD成纤维细胞对GAL和RL的不同反应揭示了细胞凋亡、细胞周期调控、细胞迁移、代谢控制和能量产生等分子通路的异常参与。总之，GAL或RL在真皮成纤维细胞中引起的代谢挑战暴露了MDD特有的mRNA和miRNA水平的适应性功能障碍。这一发现强调了挑战生物系统的必要性，以揭示疾病特有的缺陷，否则这些缺陷可能会隐藏在静止的条件下。
Major depressive disorder (MDD) is increasingly viewed as interplay of environmental stressors and genetic predisposition, and recent data suggest that the disease affects not only the brain, but the entire body. As a result, we aimed at determining whether patients with major depression have aberrant molecular responses to stress in peripheral tissues. We examined the effects of two metabolic stressors, galactose (GAL) or reduced lipids (RL), on the transcriptome and miRNome of human fibroblasts from 16 pairs of patients with MDD and matched healthy controls (CNTR). Our results demonstrate that both MDD and CNTR fibroblasts had a robust molecular response to GAL and RL challenges. Most importantly, a significant part (messenger RNAs (mRNAs): 26–33% microRNAs (miRNAs): 81–90%) of the molecular response was only observed in MDD, but not in CNTR fibroblasts. The applied metabolic challenges uncovered mRNA and miRNA signatures, identifying responses to each stressor characteristic for the MDD fibroblasts. The distinct responses of MDD fibroblasts to GAL and RL revealed an aberrant engagement of molecular pathways, such as apoptosis, regulation of cell cycle, cell migration, metabolic control and energy production. In conclusion, the metabolic challenges evoked by GAL or RL in dermal fibroblasts exposed adaptive dysfunctions on mRNA and miRNA levels that are characteristic for MDD. This finding underscores the need to challenge biological systems to bring out disease-specific deficits, which otherwise might remain hidden under resting conditions.
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影响因子：
3.7
作者：
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通讯作者：
Boominathan L
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作者：
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作者：
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