Oxygen-dependent differentiation of human keratinocytes
Oxygen-dependent differentiation of human keratinocytes
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DOI：
10.1038/sj.jid.5700522
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发表时间：
2007-02-01
影响因子：
6.5
通讯作者：
Rice, Robert H.
中科院分区：
文献类型：
--
作者：
Ngo, Mai A.;Sinitsyna, Nadezda N.;Rice, Robert H.
氧气是一种必需的微量营养素。与许多内部组织不同，人类表皮从大气中获得大部分氧气供应（21%氧气），并且通常比内部组织经历更高的氧气水平（估计约为5%）。为了测试表皮细胞的生长和分化是否依赖于这种较高的氧水平，在21%、5%和2%的氧浓度下研究了角质形成细胞培养物。与21%的氧气相比，在5%的氧气中培养对生长几乎没有影响，但导致分化程序的深度抑制，如通过分化标志物的表达和浅层中鳞片的形成所评估的。在2%的氧气中培养降低了生长速率以及分层和分化。在低氧条件下，细胞表现出增加的集落形成能力，与分化细胞的比例较低，血管内皮生长因子和环氧合酶-2的表达增加。在21%的氧气中生长导致更高水平的谷胱甘肽和氧化反应基因的表达。电泳迁移率supershift测定使用的外皮蛋白激活蛋白1（AP 1）的响应元件序列显示改变结合蛋白质的Jun和Fos家族在核提取物。因此，目前的数据表明，在人类角质形成细胞的氧依赖性分化，其中改变利用AP 1转录反应元件可能有助于。
Oxygen is an essential micronutrient. Unlike many internal tissues, human epidermis obtains much of its oxygen supply from the atmosphere (21% oxygen), and it ordinarily experiences higher oxygen levels than internal tissues (estimated approximate to 5%). To test whether epidermal cell growth and differentiation depend upon this higher oxygen level, keratinocyte cultures were studied at 21, 5, and 2% oxygen concentrations. Compared to 21% oxygen, culture in 5% had little effect on growth but led to profound suppression of the differentiation program as assessed by expression of differentiation markers and formation of squames in the superficial layers. Culture in 2% oxygen reduced the growth rate as well as stratification and differentiation. In low-oxygen conditions, the cells exhibited increased colony-forming ability, consistent with a lower proportion of differentiated cells, and increased expression of vascular endothelial growth factor and cyclooxygenase-2. Growth in 21% oxygen led to higher levels of glutathione and expression of oxidant-responsive genes. Electrophoretic mobility supershift assay using an involucrin activator protein 1 (AP1) response element sequence revealed altered binding by proteins of the Jun and Fos families in nuclear extracts. The present data thus demonstrate oxygen-dependent differentiation in human keratinocytes, to which altered utilization of AP1 transcriptional response elements may contribute.