PUVA downregulates whn expression in primary mouse keratinocytes
PUVA downregulates whn expression in primary mouse keratinocytes
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DOI：
10.1016/s1011-1344(01)00219-6
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发表时间：
2001-11-01
影响因子：
5.4
通讯作者：
Ortel, B
中科院分区：
文献类型：
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作者：
Alge, C;Baxter, RM;Ortel, B
银屑病光化学疗法（PUVA）是治疗银屑病和其他皮肤病的最有效的治疗方案之一。为了评估角质形成细胞特异性PUVA效应，我们研究了临床相关PUVA剂量对whn（裸基因）的影响。该转录因子在表皮稳态中起重要作用，并且表皮whn过度表达导致银屑病样表型。我们证明了一个持久的下调whn mRNA 48-72小时后，UVA治疗，但不单独UVA。使用转基因动物，我们也证明了剂量依赖性的whn启动子活性下调。最后，whn-null（“裸”）角质形成细胞比野生型细胞更能抵抗PUVA诱导的DNA合成抑制。我们的研究结果表明，whn抑制可能参与介导的抗增殖作用的PUVA对角质形成细胞。(C)2001爱思唯尔科技有限公司。保留所有权利。
Psoralen photochemotherapy (PUVA) is one of the most efficient treatment regimens for psoriasis and other skin diseases. In order to evaluate keratinocyte-specific PUVA effects, we investigated the impact of clinically relevant PUVA doses on whn, the 'nude' gene. This transcription factor plays an important role in epidermal homeostasis, and epidermal whn over-expression results in a psoriasis-like phenotype. We demonstrated a persistent down-regulation of whn mRNA 48-72 h after PUVA treatment but not after UVA alone. Using transgenic animals, we also demonstrated dose-dependent down-regulation of whn promoter activity. Finally, whn-null ('nude') keratinocytes were more resistant to PUVA-induced suppression of DNA synthesis than wild-type cells. Our results suggest that whn suppression may be involved in mediating the anti-proliferative effect of PUVA on keratinocytes. (C) 2001 Elsevier Science B.V. All rights reserved.