Antisense oligonucleotides inhibit vascular endothelial growth factor/vascular permeability factor expression in normal human epidermal keratinocytes.
J Invest Dermatol
; 108(4): 523-6, 1997 Apr.
Article
em En
| MEDLINE
| ID: mdl-9077485
ABSTRACT
In psoriatic lesions, epidermal keratinocytes overexpress vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) and transforming growth factor alpha (TGF-alpha). TGF-alpha has been shown to induce VEGF/VPF in normal human epidermal keratinocytes in vitro. By using a 19-mer antisense phosphorothioate oligodeoxynucleotide (PS-ODN) complementary to bases 6-24 relative to the translational start site of the VEGF/VPF mRNA, the control sense and mismatched PS-ODNs, we examined modulation of VEGF/VPF induction by TGF-alpha in vitro. Normal human epidermal keratinocytes were treated with PS-ODNs and Lipofectin for 8 h prior to the addition of TGF-alpha. Inhibition was assayed at the level of secreted protein by capture ELISA and mRNA expression was assayed by Northern blot analysis. The anti-sense PS-ODN was capable of inhibiting VEGF/VPF RNA and protein to near-basal levels. This inhibition was concentration dependent. No effect was observed with the sense or mismatch control PS-ODNs. These studies suggest that antisense oligonucleotide technology may be a potential therapy for the inhibition of angiogenesis associated with certain skin disorders such as psoriasis.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Queratinócitos
/
Fatores de Crescimento Endotelial
/
Oligonucleotídeos Antissenso
/
Linfocinas
Limite:
Humans
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos