PUVA downregulates whn expression in primary mouse keratinocytes.
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.
Alge
C
C
Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, WEL 224, 55 Fruit Street, Boston, MA 02114, USA.
Baxter
R M
RM
Doyle
M E
ME
Moor
A C
AC
Brissette
J L
JL
Ortel
B
B
D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation / Q000187:drug effects*; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D008730:Methoxsalen / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D010778:Photochemotherapy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000528:radiation effects; D001616:beta-Galactosidase / Q000235:genetics
D017931:DNA Primers; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C090140:Whn protein; D001616:beta-Galactosidase; D008730:Methoxsalen