Embryonic AP1 Transcription Factor Deficiency Causes a Collodion Baby-Like Phenotype.
Embryonic AP1 Transcription Factor Deficiency Causes a Collodion Baby-Like Phenotype.
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胚胎 AP1 转录因子缺陷导致火棉胶婴儿样表型。
DOI：
10.1016/j.jid.2017.04.032
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Rorke,EllenA
中科院分区：
文献类型：
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作者：
Young,ChristinaA;Eckert,RichardL;Adhikary,Gautam;Crumrine,Debra;Elias,PeterM;Blumenberg,Miroslav;Rorke,EllenA
AP1 转录因子是表皮基因表达的重要控制器，AP1 因子功能的改变会扰乱角质形成细胞的增殖和分化。然而，我们对 AP1 信号传导变化如何导致或加剧皮肤病的理解有限。我们已经证明，抑制成人基底上表皮中的 AP1 因子功能会导致丝聚蛋白水平降低，并导致类似于遗传性疾病寻常鱼鳞病的表型。我们现在表明，在胚胎表皮发育过程中抑制 AP1 因子功能会产生显着的表型变化，包括聚丝蛋白 mRNA 和蛋白质水平降低、屏障功能受损、超微结构显着变化以及脱水易感性增强，类似于在片尾小鼠（寻常鱼鳞病模型）中观察到的表型。此外，缺乏 AP1 因子的新生小鼠表现出火棉胶膜表型，这种表型在片尾小鼠或患有寻常鱼鳞病的新生儿个体中未观察到，但存在于其他形式的鱼鳞病中。这种混合表型表明需要更好地了解丝聚蛋白丢失和 AP1 转录因子缺乏在鱼鳞病和火棉胶膜形成中可能发挥的作用。
AP1 transcription factors are important controllers of gene expression in the epidermis, and altered AP1 factor function can perturb keratinocyte proliferation and differentiation. However, our understanding of how AP1 signaling changes may underlie or exacerbate skin disease is limited. We have shown that inhibiting AP1 factor function in suprabasal adult epidermis leads to reduced filaggrin levels and to a phenotype that resembles the genetic disorder ichthyosis vulgaris. We now show that inhibiting AP1 factor function during development in embryonic epidermis produces marked phenotypic changes including reduced filaggrin mRNA and protein levels, compromised barrier function, marked ultrastructural change, and enhanced dehydration susceptibility that resembles the phenotype observed in the flaky tail mouse, a model for ichthyosis vulgaris. In addition, the AP1 factor-deficient newborn mice display a collodion membrane phenotype that is not observed in flaky tail mice or in newborn individuals with ichthyosis vulgaris but is present in other forms of ichthyosis. This mixed phenotype suggests the need for a better understanding of the possible role of filaggrin loss and AP1 transcription factor deficiency in ichthyoses and collodion membrane formation.