Transcriptomic response of murine liver to severe injury and hemorrhagic shock: a dual-platform microarray analysis
Transcriptomic response of murine liver to severe injury and hemorrhagic shock: a dual-platform microarray analysis
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DOI：
10.1152/physiolgenomics.00020.2011
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发表时间：
2011-10-01
影响因子：
4.6
通讯作者：
Billiar, Timothy R.
中科院分区：
文献类型：
--
作者：
Edmonds, Rebecca D.;Vodovotz, Yoram;Billiar, Timothy R.
Edmonds RD、Vodovotz Y、Lagoa C、Dutta-Moscato J、Yang Y、Fink MP、Levy RM、Prince JM、Kaczorowski DJ、Tseng GC、Billiar TR。小鼠肝脏对严重损伤和失血性休克的转录组学反应：双平台微阵列分析。Physiol Genomics 43：1170-1183，2011.首次发表于2011年8月9日; doi：10.1152/physiolgenomics.00020.2011.-创伤失血性休克（HS/T）是一个复杂的过程，涉及许多分子通路。我们假设，对肝脏（一个整合免疫学和代谢的器官）的双平台微阵列分析将揭示HS/T后参与的关键途径。C57 BL/6小鼠分为5组（n = 4/组），麻醉，并手术治疗，以模拟时间过程和创伤严重度模型：1）未操作动物，2）轻微创伤，3）1.5 h失血性休克和严重创伤（HS/T），4）1.5 h HS/T，随后1 h复苏（5）1.5h HS/T +4.5h复苏（HS/T + 4.5R）。肝RNA与CodeLink和Affyssin小鼠全基因组微阵列芯片杂交。跨平台相关性>0.6的常见基因（总共2，353个基因）使用k均值聚类进行聚类，并且使用Influencity Pathways Analysis分析聚类。参与应激反应和免疫调节的基因在早期上调，并在整个实验过程中保持上调。与轻微创伤相比，细胞死亡和炎症途径相关的基因随着时间的推移以线性方式上调，并且在严重损伤中。六个簇中的三个包含参与代谢功能的基因;这些基因随着时间的推移而下调。参与氨基酸代谢以及与糖皮质激素受体、IL-6、IL-10和急性期反应相关的信号传导途径的转录物以严重程度依赖性方式升高。这是第一项使用双平台微阵列分析来检查损伤后反应的研究，揭示了可能实现新疗法或诊断的反应。
Edmonds RD, Vodovotz Y, Lagoa C, Dutta-Moscato J, Yang Y, Fink MP, Levy RM, Prince JM, Kaczorowski DJ, Tseng GC, Billiar TR. Transcriptomic response of murine liver to severe injury and hemorrhagic shock: a dual-platform microarray analysis. Physiol Genomics 43: 1170-1183, 2011. First published August 9, 2011; doi:10.1152/physiolgenomics.00020.2011.-Trauma-hemorrhagic shock (HS/T) is a complex process that elicits numerous molecular pathways. We hypothesized that a dual-platform microarray analysis of the liver, an organ that integrates immunology and metabolism, would reveal key pathways engaged following HS/T. C57BL/6 mice were divided into five groups (n = 4/group), anesthetized, and surgically treated to simulate a time course and trauma severity model: 1) nonmanipulated animals, 2) minor trauma, 3) 1.5 h of hemorrhagic shock and severe trauma (HS/T), 4) 1.5 h HS/T followed by 1 h resuscitation (HS/T + 1.0R), 5) 1.5 h HS/T followed by 4.5 h resuscitation (HS/T + 4.5R). Liver RNA was hybridized to CodeLink and Affymetrix mouse whole genome microarray chips. Common genes with a cross-platform correlation >0.6 (2,353 genes in total) were clustered using k-means clustering, and clusters were analyzed using Ingenuity Pathways Analysis. Genes involved in the stress response and immunoregulation were upregulated early and remained upregulated throughout the course of the experiment. Genes involved in cell death and inflammatory pathways were upregulated in a linear fashion with elapsed time and in severe injury compared with minor trauma. Three of the six clusters contained genes involved in metabolic function; these were downregulated with elapsed time. Transcripts involved in amino acid metabolism as well as signaling pathways associated with glucocorticoid receptors, IL-6, IL-10, and the acute phase response were elevated in a severity-dependent manner. This is the first study to examine the postinjury response using dual-platform microarray analysis, revealing responses that may enable novel therapies or diagnostics.