Reversal of epidermal hyperproliferation in psoriasis by insulin-like growth factor I receptor antisense oligonucleotides
| Autor: | Paul J. White, Stephanie R. Edmondson, Christopher J. Wraight, Sandra C. McKean, Daryl J. Venables, Ingrid J. Liepe, George A. Werther, Rhys Fogarty |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Keratinocytes
Injections Intradermal Receptor expression medicine.medical_treatment Transplantation Heterologous Biomedical Engineering Mice Nude Bioengineering Biology Applied Microbiology and Biotechnology Receptor IGF Type 1 Mice Psoriasis medicine Animals Humans RNA Messenger Receptor Hyperplasia integumentary system Epidermis (botany) Growth factor Skin Transplantation Oligonucleotides Antisense medicine.disease Molecular biology Transplantation medicine.anatomical_structure Mice Inbred CBA Molecular Medicine Epidermis Keratinocyte Biotechnology |
| Zdroj: | Nature Biotechnology. 18:521-526 |
| ISSN: | 1546-1696 1087-0156 |
| DOI: | 10.1038/75382 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|