Rogers James V, McDougal James N, Price Jennifer A, Reid Frances M, Graham John S
Battelle Memorial Institute, Biomedical Research Center, Columbus, Ohio 43201, USA.
Cutan Ocul Toxicol. 2008;27(3):135-60. doi: 10.1080/15569520802092054.
In military and civilian environments, serious cutaneous damage can result from thermal burns or exposure to the blistering agent sulfur mustard [bis (2-chloroethyl) sulfide; HD]. Similar therapies have historically been used to treat cutaneous thermal and HD injuries; however, the underlying molecular mechanisms of tissue damage and wound healing may differ between the types of burns. Using microarray analysis, this study assessed the transcriptional responses to cutaneous HD and thermal injury at 48 hours post-exposure to identify molecular networks and genes associated with each type of skin injury. Ventral abdominal sites on each of 4 weanling swine were exposed to 400 mul of undiluted HD or a heated brass rod (70 degrees C) for 8 minutes and 45-60 seconds, respectively. At 48 hours post-exposure, total RNA was isolated from excised skin samples and hybridized to Affymetrix GeneChip Porcine Genome Arrays (containing 20,201 genes). Both HD and thermal exposure promoted significant transcriptional changes where 290 and 267 transcripts were increased and 197 and 707 transcripts were decreased with HD and thermal exposure, respectively. HD- and thermal-injured skin expressed 149 increased and 148 decreased common transcripts. Comparison of the 10 most significantly changed biological functions for HD and thermal exposures identified 7 overlapping functional groups. Canonical pathways analysis revealed 15 separate signaling pathways containing transcripts associated with both HD and thermal exposure. Within these pathways, 5 transcripts (CXCR4, FGFR2, HMOX1, IL1R1, and TLR4) were identified as known targets for existing phase II/III clinical trial or Food and Drug Administration (FDA)-approved drugs. This study is the first to directly assess transcriptional changes in porcine skin subjected to HD or thermal injury over the same time period.
在军事和民用环境中，严重的皮肤损伤可能由热烧伤或接触起泡剂芥子气[双（2-氯乙基）硫化物；HD]引起。从历史上看，类似的疗法一直用于治疗皮肤热损伤和HD损伤；然而，组织损伤和伤口愈合的潜在分子机制在不同类型的烧伤之间可能有所不同。本研究使用微阵列分析评估了暴露后48小时皮肤HD和热损伤的转录反应，以确定与每种皮肤损伤类型相关的分子网络和基因。分别对4只断奶仔猪的腹部腹侧部位暴露于400微升未稀释的HD或加热的黄铜棒（70摄氏度）8分钟和45 - 60秒。暴露后48小时，从切除的皮肤样本中分离总RNA，并与Affymetrix GeneChip猪基因组阵列（包含20,201个基因）杂交。HD和热暴露均促进了显著的转录变化，HD暴露后分别有290个和197个转录本增加和减少，热暴露后分别有267个和707个转录本增加和减少。HD损伤和热损伤皮肤表达了149个增加和148个减少的共同转录本。对HD和热暴露最显著变化的10种生物学功能进行比较，确定了7个重叠的功能组。典型通路分析揭示了15条单独的信号通路，其中包含与HD和热暴露相关的转录本。在这些通路中，5个转录本（CXCR4、FGFR2、HMOX1、IL1R1和TLR4）被确定为现有II/III期临床试验或美国食品药品监督管理局（FDA）批准药物的已知靶点。本研究首次直接评估了同一时间段内猪皮肤受到HD或热损伤后的转录变化。
