Genistein Induces Bcl-2 Expression in Human Dermal Microvascular Endothelial Cells: a Short Report

Lachová, V.; Mitrengová, P.; Melegová, N.; Smetana, K.; Gál, Peter

doi:10.14712/fb2020066040142

Folia Biologica > Archive > 2020, Vol. 66 > Issue 4 > Genistein Induces Bcl-2 Expression in…

Fol. Biol. 2020, 66, 142-147

https://doi.org/10.14712/fb2020066040142

Genistein Induces Bcl-2 Expression in Human Dermal Microvascular Endothelial Cells: a Short Report

V. Lachová¹, P. Mitrengová¹, N. Melegová^2,3, K. Smetana, Jr.^4,5, Peter Gál^3,6,7

¹Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic
²Department of Pharmacology, Faculty of Medicine, Pavol Jozef Šafárik University, Košice, Slovak Republic
³Laboratory of Cell Interactions, Center of Clinical and Preclinical Research MediPark, Pavol Jozef Šafárik University, Košice, Slovak Republic
⁴BIOCEV, Vestec, Czech Republic 6Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., Košice, Slovak Republic
⁵Institute of Anatomy, First Faculty of Medicine, Charles University, Prague, Czech Republic
⁶Department of Biomedical Research, East-Slovak Institute of Cardiovascular Diseases, Inc., Košice, Slovak Republic
⁷Prague Burn Centre, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czech Republic

Received September 2020
Accepted November 2020

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.

Keywords

wound healing, angiogenesis, hormone replacement therapy, phytoestrogen.

Funding

This study was supported by the Slovak Research and Development Agency (project No. APVV-16-0207), Charles University (PROGRES Q28 and Q37), project Medical University Science Park in Košice (MediPark, Košice – Phase II) ITMS2014+313011D103 supported by the Operational Programme Research & Innovations, funded by the ERDF, and by project Centre for Tumour Ecology (CZ.02.1.01/0.0/0.0/16_019/0000785) of the Ministry of Education, Youth and Sports of the Czech Republic.