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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

Authors

  • G.J. Leirós,

    1. Fundación Pablo Cassará, Instituto de Ciencia y Tecnología Dr César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468 (C1440FFX), Ciudad de Buenos Aires, Argentina
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  • A.I. Attorresi,

    1. Fundación Pablo Cassará, Instituto de Ciencia y Tecnología Dr César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468 (C1440FFX), Ciudad de Buenos Aires, Argentina
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  • M.E. Balañá

    1. Fundación Pablo Cassará, Instituto de Ciencia y Tecnología Dr César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468 (C1440FFX), Ciudad de Buenos Aires, Argentina
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  • Funding sources
    G.J.L. was supported by a postdoctoral fellowship from CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas). M.E.B. is member of CONICET. This work was supported in part by grants provided by FONCYT (PICT2006-00874 Préstamo BID 1728/OC – AR) and by CONICET (PIP2010-2012 11220090100881).

  • Conflicts of interest
    None declared.

María Eugenia Balañá.
E-mail: mbalana@fundacioncassara.org.ar

Abstract

Summary 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.

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