Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect
Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect
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DOI：
10.1016/j.taap.2008.09.020
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发表时间：
2009-01-15
影响因子：
3.8
通讯作者：
Georgopoulos, Panos G.
中科院分区：
文献类型：
--
作者：
Gerecke, Donald R.;Chen, Minjun;Georgopoulos, Panos G.
硫芥（HD、SM）是一种化学战剂，可在数小时内引起皮肤真皮-表皮交界处大范围起泡。为了更好地了解 SM 引起的水疱的进展，在单次高剂量 SM 暴露后对小鼠皮肤进行基因表达谱分析。在 SM 暴露后的早期和晚期收集小鼠耳朵的穿刺活检（之前的研究仅考虑早期时间段）。检查活检组织是否存在病理紊乱，并使用 Affymetrix 微阵列分析系统进一步分析样品的基因表达谱。使用 ArrayTrack 进行的不同表达基因的主成分分析和层次聚类分析显示各组之间存在明显的分离。采用 KEGG 文库和 Ingenuity Pathway Analysis (IPA) 进行的通路分析表明，细胞因子-细胞因子受体相互作用、细胞粘附分子 (CAMS) 和造血细胞谱系是不同时间点受影响的常见通路。基因本体分析确定了最显着改变的生物过程为免疫反应、炎症反应和趋化性；这些发现与其他报告的较短时期的结果一致。选择选定的基因进行 RT-PCR 验证，并显示微阵列总体趋势的相关性。检查白细胞介素 1 β 进行生物分析，以确认与相应微阵列数据相关的蛋白质的存在。评估了基质金属蛋白酶抑制剂 MMP-2/MMP-9 抑制剂 1 对 SM 暴露的影响。这些结果有助于了解SM引起起泡的分子机制，以及测试不同抑制剂的功效。 (C) 2008 Elsevier Inc. 保留所有权利。
Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal-epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMS), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor 1, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors. (C) 2008 Elsevier Inc. All rights reserved.