Ap. Smyth et al., ANTISENSE OLIGONUCLEOTIDES INHIBIT VASCULAR ENDOTHELIAL GROWTH FACTOR-VASCULAR PERMEABILITY FACTOR EXPRESSION IN NORMAL HUMAN EPIDERMAL-KERATINOCYTES, Journal of investigative dermatology, 108(4), 1997, pp. 523-526
In psoriatic lesions, epidermal keratinocytes overexpress vascular end
othelial growth factor/vascular permeability factor (VEGF/VPF) and tra
nsforming 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 translal tional start si
te of the VEGF/VPF mRNA, the control sense and mismatched PS-ODNs, we
examined modulation of VEGF/VPF induction by TGE-alpha in vitro. Norma
l human epidermal keratinocytes were treated with PS-ODNs and Lipofect
in 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 capab
le of inhibiting VEGF/VPF RNA and protein to near-basal levels. This i
nhibition was concentration dependent. No effect was observed with the
sense or mismatch control PS-ODNs. These studies suggest that antisen
se oligonucleotide technology may be a potential therapy for the inhib
ition of angiogenesis associated with certain skin disorders such as p
soriasis.