Genistein does not inhibit TGF-beta1-induced conversion of human dermal fibroblasts to myofibroblasts.

Transforming growth factor beta 1 (TGF-beta1) is a pro-fibrotic cytokine with a key role in wound repair and regeneration, including induction of fibroblast-to-myofibroblast transition. Genistein is a naturally occurring selective estrogen receptor modulator with promising anti-fibrotic properties. In the present study we aimed to investigate whether genistein modulates TGF-beta1 (canonical and non-canonical) signaling in normal dermal fibroblasts at the protein level (Western blot and immunofluorescence). We demonstrated that TGF-beta1 induces the myofibroblast-like phenotype in the studied fibroblast signaling via canonical (SMAD) and non-canonical (AKT, ERK1/2, ROCK) pathways. Genistein induced only ERK1/2 expression, whereas the combination of TGF-beta1 and genistein attenuated the ERK1/2 and ROCK signaling. Of note, the other studied pathways remained almost unaffected. From this point of view, genistein does not impair conversion of normal fibroblasts to myofibroblast-like cells.

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

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-ß 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-ß) has to be answered in further studies using a model of gene silencing or genetically modified cells.