Hair follicle stem cell differentiation is inhibited through a cross talk between Wnt/â-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia.

GUSTAVO JOSE; LEIROS; ATTORRESI ALEJANDRA; BALAÑÁ , MARIA EUGENIA

BRITISH JOURNAL OF DERMATOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012 vol. 166 p. 1035 - 1042

0007-0963

Background Hair follicle (HF) regeneration begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. Wnt ⁄b-catenin signalling is known to affect mammalian hair growth positively. In androgenetic alopecia (AGA), androgens cause HF miniaturization through a mechanism that remains unclear. Circulating androgens act on DPC and alter paracrine factors that influence hair epithelial cells. Objectives To elucidate the role of androgens in dermal papilla-induced differentiation of HF stem cells. Methods HF stem cell differentiation was evaluated in a coculture model with DPC or culturing with media conditioned by DPC after activation of androgen and Wnt ⁄b-catenin signalling pathways. To study the molecular cross-talk between the androgen and Wnt signalling pathway in DPC, we analysed the expression and activation of downstream Wnt signalling molecules in the presence of androgens. Results In a coculture model with human DPC from patients with AGA and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 expression. Wnt signalling activation restored the ability of androgen-treated DPC to induce differentiation. Androgen treatment revealed a significant decrease in the cytoplasmic ⁄total b-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3b in DPC, indicative of canonical Wnt pathway inhibition. Conclusions These results suggest that androgens deregulate DPC-secreted factors involved in normal HF stem cell differentiation via the inhibition of the canonical Wnt signalling pathway.