Rao Rohit, Yang Qian, Orman Mehmet A, Berthiaume Francois, Ierapetritou Marianthi G, Androulakis Ioannis P
Chemical and Biochemical Engineering Department, Rutgers, The State University of New Jersey Piscataway, NJ 08854, USA.
Biomedical Engineering Department, Rutgers, The State University of New Jersey Piscataway, NJ 08854, USA.
Int J Burns Trauma. 2016 Jun 1;6(2):12-25. eCollection 2016.
Circadian rhythms play an important role in maintaining homeostasis and solid organ function. The purpose of this study is to assess the implications of burn injury in rats on the underlying circadian patterns of gene expression in liver. Circadian-regulated genes and burn-induced genes were identified by applying consensus clustering methodology to temporally differentially expressed probe sets obtained from burn and sham-burn data sets. Of the liver specific genes which we hypothesize that exhibit circadian rhythmicity, 88% are not differentially expressed following the burn injury. Specifically, the vast majority of the circadian regulated-genes representing central carbon and nitrogen metabolism are "up-regulated" after the burn injury, indicating the onset of hypermetabolism. In addition, cell-cell junction and membrane structure related genes showing rhythmic behavior in the control group were not differentially expressed across time in the burn group, which could be an indication of hepatic damage due to the burn. Finally, the suppression of the immune function related genes is observed in the postburn phase, implying the severe "immunosuppression". Our results demonstrated that the short term response (24-h post injury) manifests a loss of circadian variability possibly compromising the host in terms of subsequent challenges.
昼夜节律在维持体内平衡和实体器官功能方面发挥着重要作用。本研究的目的是评估大鼠烧伤对肝脏潜在昼夜基因表达模式的影响。通过将共识聚类方法应用于从烧伤和假烧伤数据集中获得的时间差异表达探针集，鉴定出昼夜调节基因和烧伤诱导基因。在我们假设表现出昼夜节律性的肝脏特异性基因中，88%在烧伤后没有差异表达。具体而言，绝大多数代表中心碳和氮代谢的昼夜调节基因在烧伤后“上调”，表明高代谢的开始。此外，在对照组中表现出节律行为的细胞间连接和膜结构相关基因在烧伤组中随时间没有差异表达，这可能是烧伤导致肝损伤的一个迹象。最后，在烧伤后阶段观察到免疫功能相关基因的抑制，这意味着严重的“免疫抑制”。我们的结果表明，短期反应（受伤后24小时）表现出昼夜变异性的丧失，这可能在随后的挑战方面损害宿主。
