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Inhibitory Effects of Retinoids on Vascular Endothelial Growth Factor Production by Cultured Human Skin Keratinocytes

Background: Vascular endothelial growth factor (VEGF), a potent angiogenic factor and vasodilator, is strongly expressed by epidermal keratinocytes in many angiogenesis-dependent skin disorders. Retinoids may modulate VEGF in skin and this may be related to an effect on rosacea. Aim: To investigate the effect of retinaldehyde on VEGF production by human keratinocytes. Methods: The effects of different concentrations of retinoids (all-trans-retinal and all-trans-retinoic acid) on VEGF production by cultured human skin keratinocytes in both cell extracts and supernatants were determined. Expression of VEGF was analyzed by enzyme-linked immunosorbent assay (ELISA) and RT-PCR. Results: The amount of cell-associated and secreted VEGF strongly decreased with retinoid concentration (e.g. 48, 69% inhibition at 0.1 µM all-trans-retinal and -retinoic acid, respectively, in the supernatants). In parallel, approximately 25% inhibition of VEGF mRNA expression was obtained in the presence of 0.01 µM all-trans-retinal. Conclusion: The decrease in VEGF expression by keratinocytes on contact with retinoids may prevent skin neoangiogenesis in certain skin diseases.