Integrative miRNA-mRNA profiling of adipose tissue unravels transcriptional circuits induced by sleep fragmentation.
Integrative miRNA-mRNA profiling of adipose tissue unravels transcriptional circuits induced by sleep fragmentation.
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DOI：
10.1371/journal.pone.0037669
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gozal D
中科院分区：
文献类型：
--
作者：
Gharib SA;Khalyfa A;Abdelkarim A;Bhushan B;Gozal D
阻塞性睡眠呼吸暂停（OSA）是一种常见的疾病，与代谢紊乱密切相关。睡眠片段化（SF）是OSA的主要后果，但其对OSA相关发病率的影响尚不清楚。我们假设SF引起内脏脂肪细胞转录网络的特定扰动，导致全身代谢紊乱。我们同时分析了在睡眠期间暴露于6小时SF的小鼠的内脏脂肪组织mRNA和miRNA表达，并开发了一种新的基于基因集富集和网络分析的计算框架来合并这些数据。这种方法利用已知的基因产物相互作用和生物途径来询问大规模的基因表达谱数据。我们发现SF诱导了几种不同途径的激活，包括参与胰岛素调节和糖尿病的途径。我们的综合方法确定了SF期间代谢反应的假定控制器和调节器。我们在功能上验证了我们的研究结果，证明改变葡萄糖和脂质稳态睡眠片段小鼠。这是第一项将睡眠片段化与内脏脂肪组织转录组的广泛破坏联系起来的研究，并提出了一种整合mRNA-miRNA信息以系统映射调控网络的可推广方法。
Obstructive sleep apnea (OSA) is a prevalent condition and strongly associated with metabolic disorders. Sleep fragmentation (SF) is a major consequence of OSA, but its contribution to OSA-related morbidities is not known. We hypothesized that SF causes specific perturbations in transcriptional networks of visceral fat cells, leading to systemic metabolic disturbances. We simultaneously profiled visceral adipose tissue mRNA and miRNA expression in mice exposed to 6 hours of SF during sleep, and developed a new computational framework based on gene set enrichment and network analyses to merge these data. This approach leverages known gene product interactions and biologic pathways to interrogate large-scale gene expression profiling data. We found that SF induced the activation of several distinct pathways, including those involved in insulin regulation and diabetes. Our integrative methodology identified putative controllers and regulators of the metabolic response during SF. We functionally validated our findings by demonstrating altered glucose and lipid homeostasis in sleep-fragmented mice. This is the first study to link sleep fragmentation with widespread disruptions in visceral adipose tissue transcriptome, and presents a generalizable approach to integrate mRNA-miRNA information for systematic mapping of regulatory networks.
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影响因子：
14.9
作者：
Jensen LJ;Kuhn M;Stark M;Chaffron S;Creevey C;Muller J;Doerks T;Julien P;Roth A;Simonovic M;Bork P;von Mering C
通讯作者：
von Mering C
DOI：
10.1161/atvbaha.111.226696
发表时间：
2011-11-01
影响因子：
8.7
作者：
Fichtlscherer, Stephan;Zeiher, Andreas M.;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
64.8
作者：
Hartwell, LH;Hopfield, JJ;Murray, AW
通讯作者：
Murray, AW