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Transforming growth factor‐β1 and ultraviolet A1 radiation increase production of vascular endothelial growth factor but not endothelin‐1 in human dermal fibroblasts
Author(s) -
Trompezinski S.,
Pernet I.,
Mayoux C.,
Schmitt D.,
Viac J.
Publication year - 2000
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2000.03707.x
Subject(s) - vascular endothelial growth factor , transforming growth factor , angiogenesis , endothelin 1 , growth factor , chemistry , fibroblast , endocrinology , medicine , microbiology and biotechnology , biology , in vitro , biochemistry , vegf receptors , receptor
Background Normal and dysregulated wound healing involves fibroblast activation and angiogenesis, in which polypeptide factors such as transforming growth factor (TGF)‐β, vascular endothelial growth factor (VEGF) and endothelin‐1 (ET‐1) play an important part. Ultraviolet (UV) A1 (365 nm) has recently received attention as a possible treatment for some dermal fibrotic disorders. Objectives The aim of this study was to evaluate the effects of TGF‐β1 and UVA1 radiation, as well as that of cobalt chloride, reported to mimic hypoxia both in vivo and in vitro , on the expression of VEGF and ET‐1 by cultured human dermal fibroblasts. Methods Levels of VEGF and ET‐1 were measured by enzyme‐linked immunosorbent assay and expression of neutral endopeptidase (NEP, CD10), known to degrade ET‐1, was quantified by flow cytometric analysis after cell trypsinization. Results Our results showed that the cells released minor amounts of VEGF and ET‐1. Both TGF‐β1 and UVA1 strongly increased VEGF secretion in a dose‐ and time‐dependent manner, without significantly affecting ET‐1 release. Irradiation of TGF‐β1‐stimulated fibroblasts resulted in a synergistic effect on increasing levels of VEGF but not ET‐1 after 48 h. Cobalt chloride stimulated the secretion of VEGF by fibroblasts; the effects of TGF‐β1 and cobalt were additive. However, no significant effect of cobalt chloride on ET‐1 secretion was observed, suggesting that ET‐1 production in fibroblasts is not oxygen‐sensitive. The expression of NEP was not modified by TGF‐β1 or UVA1 radiation. Addition of a neutralizing anti‐CD10 antibody to fibroblast cultures downregulated CD10 expression at the cell surface without changing ET‐1 levels in cell supernatants after 24 or 48 h. This suggests that membrane‐bound NEP has minimal or no activity against secreted ET‐1. Conclusions Taken together, these results underline the major role played by TGF‐β1 in increasing VEGF secretion by fibroblasts. This, as well as the documented effect of UVA1 on increasing VEGF production, may have implications for wound healing in vivo .