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.


OBJECTIVE
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 microM 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 microM all-trans-retinal.


CONCLUSIONS
The decrease in VEGF expression by keratinocytes on contact with retinoids may prevent skin neoangiogenesis in certain skin diseases.
Lachgar
S
S
Laboratoire de Biologie Cellulaire Cutanée, Institut de Recherche Pierre-Fabre, Faculté de Médecine Rangueil, Toulouse, France.
Charvéron
M
M
Gall
Y
Y
Bonafé
J L
JL
D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007641:Keratolytic Agents / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D012172:Retinaldehyde / Q000494:pharmacology; D012176:Retinoids / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007641:Keratolytic Agents; D008222:Lymphokines; D012176:Retinoids; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014212:Tretinoin; D012172:Retinaldehyde