Reduced folate carrier (RFC-1) gene expression in normal and psoriatic skin

Eli Sprecher*, Reuven Bergman, Hannah Sprecher, Gila Maor, Irena Reiter, Norberto Krivoy, Stavit Drori, Yehuda G. Assaraf, Rachel Friedman-Birnbaum

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Methotrexate is widely used in the treatment of severe psoriasis. However, little is currently known about the mechanisms underlying its therapeutic activity in the skin. Methotrexate has been shown to be carried into cells through the reduced folate carrier (RFC-1). The recent cloning and characterization of the human gene encoding this transmembranal carrier enabled us to investigate RFC-1 gene expression in human skin. Biopsies were obtained from the skin of healthy and psoriatic volunteers. RNA extracted from these biopsies was analyzed by the reverse transcriptase-polymerase chain reaction technique. While RFC-1 gene expression was barely detectable in the uninvolved skin of psoriatic patients and in the skin of healthy volunteers, high levels of RFC-1 transcripts were found in biopsies obtained from psoriatic plaques. To further investigate this pattern of gene expression, we studied skin biopsies by in situ hybridization with a labeled antisense riboprobe specific for the RFC-1 gene. The RFC-1 gene was found to be weakly expressed in the epidermis, in biopsies obtained from the skin of healthy subjects as well as in those from the uninvolved skin of psoriatic patients. In contrast, in biopsies obtained from psoriatic plaques, high levels of RFC-1 gene transcripts were found mostly in the spinous layer of the epidermis. These results suggest the existence of a specific methotrexate carrier in the human epidermis, and may bear relevance to the cutaneous manifestations of methotrexate toxicity.

Original languageEnglish
Pages (from-to)656-660
Number of pages5
JournalArchives of Dermatological Research
Volume290
Issue number12
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Methotrexate
  • Psoriasis
  • Reduced folate carrier
  • Skin

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