PUVA downregulates whn expression in primary mouse keratinocytes

Psoralen photochemotherapy (PUVA) is one of the most efficient treatment re gimens for psoriasis and other skin diseases. In order to evaluate keratino cyte-specific PUVA effects, we investigated the impact of clinically releva nt PUVA doses on whn, the 'nude' gene. This transcription factor plays an i mportant role in epidermal homeostasis, and epidermal whn over-expression r esults in a psoriasis-like phenotype. We demonstrated a persistent down-reg ulation of whn mRNA 48-72 h after PUVA treatment but not after UVA alone. U sing transgenic animals, we also demonstrated dose-dependent down-regulatio n of whn promoter activity. Finally, whn-null ('nude') keratinocytes were m ore resistant to PUVA-induced suppression of DNA synthesis than wild-type c ells. 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.