Gene expression profiling of experimental traumatic spinal cord injury as a function of distance from impact site and injury severity
Gene expression profiling of experimental traumatic spinal cord injury as a function of distance from impact site and injury severity
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DOI：
10.1152/physiolgenomics.00081.2005
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发表时间：
2005-08-11
影响因子：
4.6
通讯作者：
Faden, AI
中科院分区：
文献类型：
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作者：
De Biase, A;Knoblach, SM;Faden, AI
基因表达的变化导致脊髓损伤（SCI）后的病理生理学改变。我们检测了大鼠轻度、中度或重度挫伤 SCI 后撞击部位以及头侧和尾侧区域随时间（4 小时、24 小时、7 天）的基因表达。使用高密度寡核苷酸微阵列，其中包括相似的 27,000 个基因/EST（Affymetrix RG-U34；A、B 和 C 阵列）以及多重分析（MAS 5.0、dChip）。轻度损伤后的变化相对较快（4和24小时），而重度损伤后变化则延迟且延长（24小时和7天）。中度损伤后，基因表达变化的数量和幅度在损伤部位最大，并且随着损伤严重程度的变化，在头侧和尾侧区域增加。假手术导致与轻度损伤相似的表达变化，这表明使用时间相关的手术对照以及幼稚动物进行此类研究的重要性。许多基因和 EST 的表达发生了改变；这些根据本体论进行功能分类。这些功能类别的总体表现随着距损伤部位的距离和损伤严重程度的不同而变化，促成每个功能类别的个体基因也是如此。使用不同的聚类方法来识别神经元特异性基因和一些以前与 SCI 无关的转录因子的变化。这项研究代表了迄今为止对 SCI 后基因表达变化最全面的评估。结果强调了微阵列方法在揭示整体基因组反应以及在继发性损伤级联中可能重要的特定基因簇和/或家族的变化方面的能力。
Changes in gene expression contribute to pathophysiological alterations following spinal cord injury (SCI). We examined gene expression over time (4 h, 24 h, 7 days) at the impact site, as well as rostral and caudal regions, following mild, moderate, or severe contusion SCI in rats. High-density oligonucleotide microarrays were used that included similar to 27,000 genes/ESTs (Affymetrix RG-U34; A, B and C arrays), together with multiple analyses ( MAS 5.0, dChip). Alterations after mild injury were relatively rapid (4 and 24 h), whereas they were delayed and prolonged after severe injury (24 h and 7 days). The number and magnitude of gene expression changes were greatest at the injury site after moderate injury and increased in rostral and caudal regions as a function of injury severity. Sham surgery resulted in expression changes that were similar to mild injury, suggesting the importance of using time-linked surgical controls as well as naive animals for these kinds of studies. Expression of many genes and ESTs was altered; these were classified functionally based on ontology. Overall representation of these functional classes varied with distance from the site of injury and injury severity, as did the individual genes that contributed to each functional class. Different clustering approaches were used to identify changes in neuronal-specific genes and several transcription factors that have not previously been associated with SCI. This study represents the most comprehensive evaluation of gene expression changes after SCI to date. The results underscore the power of microarray approaches to reveal global genomic responses as well as changes in particular gene clusters and/or families that may be important in the secondary injury cascade.