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Br J Dermatol. 2012 May;166(5):1035-42. doi: 10.1111/j.1365-2133.2012.10856.x.

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

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1
Fundación Pablo Cassará, Instituto de Ciencia y Tecnología Dr César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad de Buenos Aires, Argentina.

Abstract

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/β-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/β-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 β-catenin protein ratio and upregulation of the activity of glycogen synthase kinase-3β 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.

[Indexed for MEDLINE]

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