Klf4 is a transcription factor required for establishing the barrier function of the skin
Klf4 is a transcription factor required for establishing the barrier function of the skin
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DOI：
10.1038/11926
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发表时间：
1999-08-01
期刊：
影响因子：
30.8
通讯作者：
Fuchs, E
中科院分区：
文献类型：
--
作者：
Segre, JA;Bauer, C;Fuchs, E
表皮位于身体和环境之间的界面，必须保护身体免受有毒物质和脱水的影响，并保护自己免受物理和机械应力的影响（1-4）。在出生前和表皮分化的最后阶段获得，皮肤的蛋白质/脂质屏障创造了保护动物免受微生物感染和脱水所必需的表面密封。我们在这里表明，Kruppel样因子4（Klf 4，由基因Klf 4编码），在表皮的分化层中高度表达，是至关重要的和选择性的屏障收购。Klf 4（-/-）小鼠出生后不久由于皮肤屏障功能的丧失而死亡，如通过外部染料的渗透和体液的快速损失所测量的。通过将Klf 4（-/-）皮肤移植到裸鼠上不能纠正该缺陷。屏障的丧失发生在对表皮的众所周知的结构特征没有形态学和生物化学改变的情况下，这些结构特征对于机械完整性是必不可少的。相反，晚期分化结构被选择性地扰乱，包括皮质包膜，这是脂质组织的可能支架。使用抑制性消减杂交，我们确定了三个转录本编码的皮质包膜蛋白与Klf 4的情况下改变表达。Sprr 2a是其中之一，并且是已知其启动子具有功能性Klf 4结合位点的唯一表皮基因。我们的研究为屏障功能的转录调控提供了新的见解，并为解开协调这一重要过程的分子事件铺平了道路。
Located at the interface between body and environment, the epidermis must protect the body against toxic agents and dehydration, and protect itself against physical and mechanical stresses(1-4). Acquired just before birth and at the last stage of epidermal differentiation, the skin's proteinaceous/lipid barrier creates a surface seal essential for protecting animals against microbial infections and dehydration. We show here that Kruppel-like factor 4 (Klf4, encoded by the gene Klf4), highly expressed in the differentiating layers of epidermis, is both vital to and selective for barrier acquisition. Klf4(-/-) mice die shortly after birth due to loss of skin barrier function, as measured by penetration of external dyes and rapid loss of body fluids. The defect was not corrected by grafting of Klf4(-/-) skin onto nude mice. Loss of the barrier occurs without morphological and biochemical alterations to the well-known structural features of epidermis that are essential for mechanical integrity. Instead, late-stage differentiation structures are selectively perturbed, including the cornified envelope, a likely scaffold for lipid organization. Using suppressive subtractive hybridization, we identified three transcripts encoding cornified envelope proteins with altered expression in the absence of Klf4. Sprr2a is one, and is the only epidermal gene whose promoter is known to possess a functional Klf4 binding site. Our studies provide new insights into transcriptional governance of barrier function, and pave the way for unravelling the molecular events that orchestrate this essential process.