Ectopic expression of Kruppel like factor 4 (Klf4) accelerates formation of the epidermal permeability barrier
Ectopic expression of Kruppel like factor 4 (Klf4) accelerates formation of the epidermal permeability barrier
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DOI：
10.1242/dev.00477
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发表时间：
2003-06-01
期刊：
影响因子：
4.6
通讯作者：
Segre, JA
中科院分区：
文献类型：
--
作者：
Jaubert, J;Cheng, J;Segre, JA
表皮渗透屏障功能障碍会导致脱水、电解质失衡和体温调节不良。未成熟的皮肤是感染性病原体和局部使用物质中潜在毒素的进入门户。由于皮肤是子宫内最后成熟的器官之一，因此妊娠 34 周之前出生的早产儿出现并发症的风险很大。通过靶向消融，转录因子 kruppel 样因子 4 (Klf4) 在屏障获取中具有重要功能。我们研究了 Klf4 在子宫内的表达是否足以建立表皮屏障。具体来说，当与从表皮角蛋白5启动子表达四环素反式激活子tTA的转基因小鼠杂交时，我们产生了从四环素诱导型启动子表达Klf4的小鼠品系。这些小鼠在发育过程中比对照组早一天排除染料溶液，从而表现出屏障获取加速。这种染料不渗透性的基础是形态变化，包括分层数量的增加、终末分化标记的表达和角质化包膜的组装。从所有标准来看，Klf4 异位表达都会加速终末分化的正常过程。这些小鼠的过早屏障获得遵循正常模式，而不是转基因启动子的模式，表明 KLF4 发挥作用的能力范围。尽管其他转基因小鼠扰乱了屏障的获得，但这些小鼠是第一个加速屏障建立过程的小鼠。这些研究表明KLF4调节屏障获得，并为研究如何加速早产儿屏障获得过程提供了动物模型。
Dysfunction of the epidermal permeability barrier can result in dehydration, electrolyte imbalance and poor thermoregulation. Immature skin is a portal of entry for infectious agents and potential toxins in topically applied substances. As the skin is one of the last organs to mature in utero, premature infants born before 34 weeks gestation are at great risk for complications. The transcription factor kruppel-like factor 4 (Klf4), has been shown by a targeted ablation, to have an essential function in barrier acquisition. We investigated whether Klf4 expression in utero is sufficient to establish the epidermal barrier. Specifically, we generated lines of mice that express Klf4 from a tetracycline inducible promoter when crossed with transgenic mice expressing the tetracycline transactivator tTA from the epidermal keratin 5 promoter. These mice exhibit acceleration in barrier acquisition as manifest by the exclusion of a dye solution one day earlier in development than controls. Underlying this dye impermeability are morphological changes, including an increased number of stratified layers, expression of terminal differentiation markers and assembly of cornified envelopes. By all criteria, Klf4 ectopic expression accelerates the normal process of terminal differentiation. Premature barrier acquisition in these mice follows the normal pattern rather than the pattern of the transgene promoter, indicating that there are fields of competence in which KLF4 acts. Although other transgenic mice have perturbed barrier acquisition, these mice are the first to accelerate the process of barrier establishment. These studies show that KLF4 regulates barrier acquisition and provides an animal model for studying how to accelerate the process of barrier acquisition for the premature infant.