Overexpression of the Transcription Factor Yin-Yang-1 Suppresses Differentiation of HaCaT Cells in Three-Dimensional Cell Culture
Overexpression of the Transcription Factor Yin-Yang-1 Suppresses Differentiation of HaCaT Cells in Three-Dimensional Cell Culture
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DOI：
10.1038/jid.2010.229
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发表时间：
2011-01-01
影响因子：
6.5
通讯作者：
Otsuka, Fujio
中科院分区：
文献类型：
--
作者：
Taguchi, Shijima;Kawachi, Yasuhiro;Otsuka, Fujio
阴阳1（Yin-Yang-1，YY 1）是GLI-Kruppel转录因子家族的成员之一，YY 1的mRNA和蛋白质在多种组织和细胞中均有表达，提示YY 1是组成性和普遍性表达的。然而，在表皮组织中，我们以前报道，YY 1蛋白在未分化的基底角质形成细胞中高水平表达，并在向基底上层分化的过程中下调。角质形成细胞分化过程中的这种差异表达模式表明YY 1可能在调节角质形成细胞分化中起重要作用。在这项研究中，我们研究了YY 1在人角质形成细胞系HaCaT的分化中的作用，使用气液界面三维培养。YY 1在HaCaT细胞中的组成性过表达在空气压力诱导的分化导致未分化的表型，增厚的分层，抑制分化标志物的表达，并保留增殖活性。这些发现表明，YY 1可能在维持基底表皮层角质形成细胞的未分化表型中具有重要作用，并且YY 1在基底上层中表达的减少可能允许角质形成细胞分化并向表皮的上层移动。
Yin-Yang-1 (YY1) is a member of the GLI-Kruppel family of transcription factors, and both YY1 mRNA and protein expression have been identified in a number of different tissues and cell types suggesting that it is expressed both constitutively and ubiquitously. In epidermal tissue, however, we reported previously that YY1 protein is expressed at high levels in undifferentiated basal keratinocytes and is downregulated during differentiation toward the suprabasal layers. This differential expression pattern during keratinocyte differentiation suggests that YY1 may have an important role in regulating keratinocyte differentiation. In this study, we examined the role of YY1 in differentiation of the human keratinocyte cell line HaCaT using air-liquid interface three-dimensional culture. The constitutive overexpression of YY1 in HaCaT cells during air exposure-induced differentiation resulted in an undifferentiated phenotype, thickening of the stratified layers, suppression of differentiation marker expression, and retention of proliferative activity. These findings suggested that YY1 may have an important role in maintenance of the undifferentiated phenotype of keratinocytes in the basal epidermal layer, and that reduction of YY1 expression in the suprabasal layers may allow keratinocytes to differentiate and move toward the upper layers of the epidermis.