Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks.
Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks.
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DOI：
10.1016/j.isci.2018.07.022
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发表时间：
2018-09-28
期刊：
影响因子：
5.8
通讯作者：
Kuroda S
中科院分区：
文献类型：
--
作者：
Kawata K;Hatano A;Yugi K;Kubota H;Sano T;Fujii M;Tomizawa Y;Kokaji T;Tanaka KY;Uda S;Suzuki Y;Matsumoto M;Nakayama KI;Saitoh K;Kato K;Ueno A;Ohishi M;Hirayama A;Soga T;Kuroda S
胰岛素的浓度选择性地调节多种细胞功能。为了了解胰岛素浓度是如何被细胞解释的，我们使用转录组学数据、信号蛋白的蛋白质印迹分析和代谢组学数据在FAO肝癌细胞中构建了胰岛素作用的trans-omic网络。通过将敏感性整合到trans-omic网络中，我们确定了由高剂量和低剂量胰岛素刺激的选择性trans-omic网络，分别表示为诱导和基础胰岛素信号。诱导的胰岛素信号通过涉及Erk的途径选择性地传递到即刻早期和上调基因表达的增加，而基础胰岛素信号通过涉及Akt的途径选择性地传递，并且增加Foxo磷酸化和减少下调基因表达。我们通过分析胰岛素阻断的大鼠肝脏验证了体内选择性trans-omic网络。这种综合分析使人们能够从分子上了解肝细胞如何解释生理胰岛素信号以调节细胞功能。我们利用多组学数据构建了胰岛素作用的transomic网络transomic网络整合了磷酸化、转录和代谢我们根据敏感性将诱导型和基础型胰岛素依赖的transomic网络分为诱导型和基础型胰岛素触发的肝脏选择性transomic网络系统生物学;组学;代谢组学;转录组学
The concentrations of insulin selectively regulate multiple cellular functions. To understand how insulin concentrations are interpreted by cells, we constructed a trans-omic network of insulin action in FAO hepatoma cells using transcriptomic data, western blotting analysis of signaling proteins, and metabolomic data. By integrating sensitivity into the trans-omic network, we identified the selective trans-omic networks stimulated by high and low doses of insulin, denoted as induced and basal insulin signals, respectively. The induced insulin signal was selectively transmitted through the pathway involving Erk to an increase in the expression of immediate-early and upregulated genes, whereas the basal insulin signal was selectively transmitted through a pathway involving Akt and an increase of Foxo phosphorylation and a reduction of downregulated gene expression. We validated the selective trans-omic network in vivo by analysis of the insulin-clamped rat liver. This integrated analysis enabled molecular insight into how liver cells interpret physiological insulin signals to regulate cellular functions. We constructed a trans-omic network of insulin action using multi-omic data The trans-omic network integrates phosphorylation, transcription, and metabolism We divided induced- and basal-insulin-dependent trans-omic network by sensitivity Induced and basal insulin triggered selective trans-omic network in the liver Systems Biology; Omics; Metabolomics; Transcriptomics
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