Inhibition of Dermal papilla-induced Hair Follicle Stem Cells differentiation involves Glycogen synthase kinase-3¥â modulation in androgenetic alopecia

LEIRÓS GJ; ATTORRESI, AI; BALAÑA ME

Barcelona

Congreso; 41st Annual European Society for Dermatological Research Meeting; 2011

European Society for Dermatological Research

The hair follicle formation begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells (HFSC) in the bulge region. In androgenetic alopecia (AGA), circulating androgens act on sensitive DPC and alter regulatory paracrine factors probably involved in the differentiation and proliferation of the HFSC. While androgens have a regressive effect, Wnt/©¬-catenin signaling is known to positively affect mammalian hair growth. The aim of this work is to determine the role of androgens in the DPC-induced HFSC differentiation. In a co-culture model with human DPC from patients suffering AGA and HFSC, androgens treatment abrogates hair differentiation downregulating the expression of the keratin K6hf, a hair differentiation marker, in HFSC.  LiCl, which mimics the effects of Wnt signalling activation, restored the differentiation ability of androgen- treated DPC. In DPC, analysis of the cytoplasmic pool of ¥â-catenin by Western blot showed that the ratio cytoplasmatic/total ¥â-catenin is significantly lower in the presence of androgens indicating an inhibition of the canonical Wnt signalling. Glycogen synthase kinase-3¥â (GSK-3¥â) inhibits Wnt signalling by phosphorylation of ¥â-catenin. In DPC, we found that androgens activate GSK-3¥â by upregulation of its expression and also by inhibition of its phosphorylation at Ser-9. These results suggest that the activation of GSK-3¥â in the presence of androgens may inhibit canonical Wnt signaling resulting in abrogation of DPC-induced HFSC differentiation.