Light-dark oscillations in the lung transcriptome: implications for lung homeostasis, repair, metabolism, disease, and drug action.
Light-dark oscillations in the lung transcriptome: implications for lung homeostasis, repair, metabolism, disease, and drug action.
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DOI：
10.1152/japplphysiol.00079.2011
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发表时间：
2011-03
影响因子：
3.3
通讯作者：
S. Sukumaran;W. Jusko;D. DuBois;R. Almon
中科院分区：
文献类型：
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作者：
S. Sukumaran;W. Jusko;D. DuBois;R. Almon
昼夜节律或昼夜节律是生物过程中24小时的变化，是为了生物体的有效运作而进化的。这种振荡及其在许多外周组织中的调节尚不清楚。在这项研究中，我们使用Affymetrix基因芯片进行了一个丰富的时间序列实验，涉及54只动物，在24小时周期内的18个时间点被杀死，以检测大鼠肺中基因表达的光暗周期模式。数据挖掘鉴定出646个基因（由1006个探针组表示），它们在肺中表现出强劲的表达振荡，并被解析为8个不同的时间簇。令人惊讶的是，超过三分之二的探针组显示循环表达在动物的清淡/不活跃时期达到峰值。6个核心时钟基因和9个时钟相关基因在肺中的表达呈现节律性振荡。许多在非活性期达到峰值的基因包括与细胞外基质、细胞骨架、蛋白质加工和运输相关的基因，这些基因似乎主要参与器官的修复和重塑。在维持正常肺功能中起重要作用的生长因子配体及其受体编码基因也表现出节律性表达。此外，参与内源性化合物、外源药物和治疗药物的代谢和运输的基因，以及作为许多肺部疾病的生物标志物或潜在治疗靶点的基因，也表现出24小时循环振荡，表明这种节律在调节肺生理和病理生理的各个方面发挥重要作用。
Diurnal-nocturnal, or circadian-like, rhythms are 24-h variations in biological processes, evolved for the efficient functioning of living organisms. Such oscillations and their regulation in many peripheral tissues are still unclear. In this study, we used Affymetrix gene chips in a rich time-series experiment involving 54 animals killed at 18 time points within the 24-h cycle to examine light-dark cycle patterns of gene expression in rat lungs. Data mining identified 646 genes (represented by 1,006 probe sets) showing robust oscillations in expression in lung that were parsed into 8 distinct temporal clusters. Surprisingly, more than two-thirds of the probe sets showing cyclic expression peaked during the animal's light/inactive period. Six core clock genes and nine clock-related genes showed rhythmic oscillations in their expression in lung. Many of the genes that peaked during the inactive period included genes related to extracellular matrix, cytoskeleton, and protein processing and trafficking, which appear to be mainly involved in the repair and remodeling of the organ. Genes coding for growth factor ligands and their receptors, which play important roles in maintaining normal lung function, also showed rhythmic expression. In addition, genes involved in the metabolism and transport of endogenous compounds, xenobiotics, and therapeutic drugs, along with genes that are biomarkers or potential therapeutic targets for many lung diseases, also exhibited 24-h cyclic oscillations, suggesting an important role for such rhythms in regulating various aspects of the physiology and pathophysiology of lung.