It has been shown previously that oestradiol protects the vascular network, leading to increased skin flap viability associated with Bcl-2, VEGF and FGF-2 up-regulation. We have shown that genistein, a natural selective oestrogen receptor modulator, also increases skin flap viability in rats and induces Bcl-2 expression in human umbilical vein endothelial cells. In the present study we aimed to answer the question whether genistein increases expression of Bcl-2, a potent anti-apoptotic protein, in human dermal microvascular endothelial cells (HMVEC-d) as well. Our results showed that administration of genistein induces Bcl-2 expression in a concentration-dependent manner. Cell co-treatment with genistein and anti-ER compounds (MPP, PHTPP, ICI, G-15) diminished the observed positive effect of genistein on Bcl-2 expression. The decrease in Bcl-2 expression in HMVEC-d was most prominent after co-treatment with ICI (nuclear ER antagonist/ GPR30 agonist) and PHTPP (selective ER-β antagonist). In conclusion, genistein increases Bcl-2 expression in HMVEC-d, contributing to its protective effect on the skin flap viability. However, the question whether the mechanism is ER-specific (via ER-β) has to be answered in further studies using a model of gene silencing or genetically modified cells.

BIOCEV Vestec Czech Republic

Department of Biomedical Research East Slovak Institute of Cardiovascular Diseases Inc Košice Slovak Republic

Department of Pharmacognosy and Botany Faculty of Pharmacy Comenius University Bratislava Slovak Republic

Department of Pharmacology Faculty of Medicine Pavol Jozef Šafárik University Košice Slovak Republic

Institute of Anatomy 1st Faculty of Medicine Charles University Prague Czech Republic

Laboratory of Cell Interactions Center of Clinical and Preclinical Research MediPark Pavol Jozef Šafárik University Košice Slovak Republic

Prague Burn Centre 3rd Faculty of Medicine Charles University and University Hospital Královské Vinohrady Prague Czech Republic

Citace poskytuje Crossref.org

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