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皮肤和口腔黏膜创伤转录组的位置差异。

Positional differences in the wound transcriptome of skin and oral mucosa.

机构信息

Center for Wound Healing & Tissue Regeneration, University of Illinois, Chicago, IL, USA.

出版信息

BMC Genomics. 2010 Aug 12;11:471. doi: 10.1186/1471-2164-11-471.

Abstract

BACKGROUND

When compared to skin, oral mucosal wounds heal rapidly and with reduced scar formation. Recent studies suggest that intrinsic differences in inflammation, growth factor production, levels of stem cells, and cellular proliferation capacity may underlie the exceptional healing that occurs in oral mucosa. The current study was designed to compare the transcriptomes of oral mucosal and skin wounds in order to identify critical differences in the healing response at these two sites using an unbiased approach.

RESULTS

Using microarray analysis, we explored the differences in gene expression in skin and oral mucosal wound healing in a murine model of paired equivalent sized wounds. Samples were examined from days 0 to 10 and spanned all stages of the wound healing process. Using unwounded matched tissue as a control, filtering identified 1,479 probe sets in skin wounds yet only 502 probe sets in mucosal wounds that were significantly differentially expressed over time. Clusters of genes that showed similar patterns of expression were also identified in each wound type. Analysis of functionally related gene expression demonstrated dramatically different reactions to injury between skin and mucosal wounds. To explore whether site-specific differences might be derived from intrinsic differences in cellular responses at each site, we compared the response of isolated epithelial cells from skin and oral mucosa to a defined in vitro stimulus. When cytokine levels were measured, epithelial cells from skin produced significantly higher amounts of proinflammatory cytokines than cells from oral mucosa.

CONCLUSIONS

The results provide the first detailed molecular profile of the site-specific differences in the genetic response to injury in mucosa and skin, and suggest the divergent reactions to injury may derive from intrinsic differences in the cellular responses at each site.

摘要

背景

与皮肤相比,口腔黏膜伤口愈合迅速,且瘢痕形成较少。最近的研究表明,炎症、生长因子产生、干细胞水平和细胞增殖能力方面的内在差异可能是口腔黏膜异常愈合的基础。本研究旨在通过无偏倚的方法比较口腔黏膜和皮肤伤口的转录组,以确定这两个部位愈合反应的关键差异。

结果

我们使用微阵列分析,在一个配对等大小伤口的小鼠模型中研究了皮肤和口腔黏膜伤口愈合过程中基因表达的差异。在 0 至 10 天的时间内采集样本,涵盖了伤口愈合过程的所有阶段。与未受伤的匹配组织作为对照,过滤确定了皮肤伤口中 1479 个探针集,而黏膜伤口中仅 502 个探针集随时间显著差异表达。在每种伤口类型中还鉴定了具有相似表达模式的基因簇。对功能相关基因表达的分析表明,皮肤和黏膜伤口对损伤的反应截然不同。为了探究部位特异性差异是否可能源于每个部位细胞反应的内在差异,我们比较了来自皮肤和口腔黏膜的分离上皮细胞对特定体外刺激的反应。当测量细胞因子水平时,皮肤上皮细胞产生的促炎细胞因子明显高于口腔黏膜细胞。

结论

研究结果提供了黏膜和皮肤损伤后遗传反应的部位特异性差异的第一个详细分子谱,并表明对损伤的不同反应可能源自每个部位细胞反应的内在差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758d/3091667/c6632138d3a3/1471-2164-11-471-1.jpg

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