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

Abstract

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.

FK506 (Tacrolimus) Inhibition of Intracellular Production and Enhancement of Interleukin 1α through Glucocorticoid Application to Chemically Treated Human Keratinocytes

“…Vasodilators such as VEGF are expressed in epidermal KCs [5] and thus may be contributing factors for rosacea. IL-1 ␣ induces angiogenesis by activating VEGF signaling between infl ammatory and endothelial cells [11] .…”

“…M has recently been shown to enhance the chemically (2,4,6-trinitrobenzene sulfonic acid sodium salt, TNBS) induced production and gene expression of IL-1 ␣ through activation of nuclear factor B and activator protein 1 following hapten application in murine epidermal Pam cells [4] . IL-1 ␣ may induce angiogenesis by activating VEGF (vascular endothelial growth factor) [5] expressed in KCs via interactions of infl ammatory cells with endothelial cells. Thus, IL-1 ␣ would appear related to the onset of rosacea [6] , a disorder characterized by persistent erythemas and dilated blood vessels.…”

“…These agents exert not only anti-infl ammatory action as immunosuppressants but possibly may also modulate tissue repair by controlling certain infl ammatory cytokines such as IL-1 ␣ [8] and growth factors such as VEGF [5] .…”

RALGA (Diacnéal^®), a Retinaldehyde and Glycolic Acid Association and Postinflammatory Hyperpigmentation in Acne – A Review

“…RAL has revealed a retinoid-like activity in the stimulation of proliferation and differentiation, comedolysis, inhibition of protein expression (in particular melanin) and increase in epidermal thickness [24,26,27]. RAL also shows a specific antibacterial activity against Propionibacterium acnes [28,29].…”

New Syntheses of Retinal and Its Acyclic Analog γ‐Retinal by an Extended Aldol Reaction with a C6 Building Block That Incorporates a C5 Unit after Decarboxylation. A Formal Route to Lycopene and β‐Carotene

“…The decrease in vascular endothelial growth factor (VEGF) expression by keratinocytes on contact with retinal has been recently published, and the conclusions showed that the decrease in VEGF expression may prevent skin neoangiogenesis in certain skin diseases [18]. We recently reported on the syntheses of 9-methylene-and 13-methyleneretinals 1 ) [19].…”