Reversal of epidermal hyperproliferation in psoriasis by insulin-like growth factor I receptor antisense oligonucleotides

Nat Biotechnol. 2000 May;18(5):521-6. doi: 10.1038/75382.


Epidermal hyperplasia is a key feature of the common skin disorder psoriasis. Stimulation of epidermal keratinocytes by insulin-like growth factor I (IGF-I) is essential for cell division, and increased sensitivity to IGF-I may occur in psoriasis. We hypothesized that inhibition of IGF-I receptor expression in the psoriasis lesion would reverse psoriatic epidermal hyperplasia by slowing the rate of keratinocyte cell division. Here we report the use of C5-propynyl-dU,dC-phosphorothioate antisense oligonucleotides to inhibit IGF-I receptor expression in keratinocytes. We identified several inhibitory antisense oligonucleotides and demonstrated IGF-I receptor inhibition in vitro through an mRNA targeting mechanism. Repeated injection of these oligonucleotides into human psoriasis lesions, grafted onto nude mice, caused a dramatic normalization of the hyperplastic epidermis. The findings indicate that IGF-I receptor stimulation is a rate-limiting step in psoriatic epidermal hyperplasia and that IGF-I receptor targeting by cutaneous administration of antisense oligonucleotides forms the basis of a potential new psoriasis therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epidermis / pathology*
  • Humans
  • Hyperplasia
  • Injections, Intradermal
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Mice
  • Mice, Inbred CBA
  • Mice, Nude
  • Oligonucleotides, Antisense / therapeutic use*
  • Psoriasis / drug therapy*
  • RNA, Messenger / isolation & purification
  • Receptor, IGF Type 1 / analysis
  • Receptor, IGF Type 1 / genetics*
  • Skin Transplantation
  • Transplantation, Heterologous


  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Receptor, IGF Type 1