EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA SPECIFICALLY INDUCE THE ACTIVATION-ASSOCIATED AND HYPERPROLIFERATION-ASSOCIATED KERATIN-6 AND KERATIN-16
EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA SPECIFICALLY INDUCE THE ACTIVATION-ASSOCIATED AND HYPERPROLIFERATION-ASSOCIATED KERATIN-6 AND KERATIN-16
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DOI：
10.1073/pnas.90.14.6786
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发表时间：
1993-07-15
影响因子：
11.1
通讯作者：
BLUMENBERG, M
中科院分区：
文献类型：
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作者：
JIANG, CK;MAGNALDO, T;BLUMENBERG, M
表皮损伤导致角化细胞活化，角化细胞产生生长因子和细胞因子并对其作出反应，并发生迁移。活化的角化细胞表达一对特定的角蛋白，K6和K16，不同于健康表皮中的角蛋白。角质形成细胞可以被激活，例如，通过结合适当的配体到表皮生长因子受体（EGFR）。我们分析了EGFR激活对角蛋白基因转录的影响，方法是在存在或不存在EGF或转化生长因子α (TGFalpha)两种激活EGFR的生长因子的情况下，将含有与报告基因相关的角蛋白启动子的dna转染到人表皮角质形成细胞的原代培养物中。EGFR的激活对单纯上皮、基底层特异性或分化特异性角蛋白的启动子没有影响。相反，K6和K16的表达受到强烈的特异性诱导。K16基因启动子的20bp DNA片段传递了EGF调控，在异源结构中起作用，因此构成了EGF响应元件。K6启动子特异性结合该元件和类似的K6启动子序列的核蛋白。因此，EGF通过与这些角蛋白基因启动子中EGF应答元件结合的核蛋白特异性诱导活化的角质形成细胞的标记物K6和K16。
Epidermal injury results in activation of keratinocytes which produce and respond to growth factors and cytokines and become migratory. Activated keratinocytes express a specific pair of keratin proteins, K6 and K16, distinct from the keratins in the healthy epidermis. Keratinocytes can be activated, for example, by binding of the appropriate ligands to the epidermal growth factor receptor (EGFR). We have analyzed the effects of EGFR activation on keratin gene transcription by transfecting DNAs containing keratin promoters linked to a reporter gene into primary cultures of human epidermal keratinocytes in the presence or absence of EGF or transforming growth factor alpha (TGFalpha), two growth factors that activate EGFR. The activation of EGFR had no effect on the promoters of simple epithelial, basal-layer-specific, or differentiation-specific keratins. In contrast, the expression of K6 and K16 was strongly and specifically induced. A 20-bp DNA segment of the K16 gene promoter conveyed the EGF regulation, functioned in a heterologous construct, and therefore constituted an EGF-responsive element. A nuclear protein specifically bound to this element and to the analogous sequence of the K6 promoter. Thus, EGF specifically induces K6 and K16, markers of activated keratinocytes, via nuclear proteins that bind to EGF-responsive elements in the promoters of these keratin genes.