Gene expression profile of tissue engineered skin subjected to acute barrier disruption
Gene expression profile of tissue engineered skin subjected to acute barrier disruption
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DOI：
10.1046/j.1523-1747.2003.12364.x
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发表时间：
2003-08-01
影响因子：
6.5
通讯作者：
Andreadis, ST
中科院分区：
文献类型：
--
作者：
Koria, P;Brazeau, D;Andreadis, ST
皮肤的主要功能是保护身体免受感染，脱水，和其他环境的侮辱，通过创造一个不可渗透的屏障的角质细胞层，角质层。与培养中的细胞相比，组织工程皮肤等同物含有发育良好的基底、棘、颗粒和皮质细胞层，为研究组织对屏障破坏的反应提供了极好的模型。在气液界面培养7 d后，通过短时间暴露于丙酮破坏组织屏障，并使用DNA微阵列评估组织的整体基因表达谱。我们发现，组织工程皮肤响应屏障破坏的两波动态响应。早期，细胞上调信号转导、应激、增殖和炎症基因，以保护组织，并可能将损伤传递给免疫系统和邻近组织。在以后的时间，促炎细胞因子和一些生长相关基因显着减少，但参与脂质合成的酶增加，表明表皮细胞试图恢复失去的屏障。增殖抗原Ki67的定量免疫染色显示，丙酮的屏障破坏增加了4倍，与微阵列数据和以前的体内研究一致的增殖。我们的工作表明，功能基因组学可用于组织工程，以了解组织发育，伤口再生，并对环境刺激的反应。在分子水平上更好地理解工程组织可能有助于其在临床上的应用和作为毒理学检测的生物传感器。
The main function of the skin is to protect the body from infection, dehydration, and other environmental insults by creating an impermeable barrier of cornified cell layers, the stratum corneum. In contrast to cells in culture, tissue-engineered skin equivalents contain well-developed basal, spinous, granular, and cornified cell layers providing an excellent model to study the tissue response to barrier disruption. After 7 d of culture at the air-liquid interface the barrier of the tissues was disrupted by short exposure to acetone and the global gene expression profile of the tissues was evaluated using DNA microarrays. We found that tissue-engineered skin responds to barrier disruption by a two-wave dynamic response. Early on, the cells upregulate signal transducing, stress, proliferation, and inflammation genes to protect the tissue and possibly to communicate the damage to the immune system and neighboring tissues. At later times, pro-inflammatory cytokines and some growth-related genes are significantly reduced but enzymes that participate in lipid synthesis increase, suggesting that the epidermal cells attempt to restore the lost barrier. Quantitative immunostaining for the proliferation antigen Ki67 revealed that barrier disruption by acetone increased proliferation by 4-fold in agreement with the microarray data and previous in vivo studies. Our work suggests that functional genomics may be used in tissue engineering to understand tissue development, wound regeneration, and response to environmental stimuli. A better understanding of engineered tissues at the molecular level may facilitate their application in the clinic and as biosensors for toxicologic testing.