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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.
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.
Leirós GJ, Attorresi AI, Balañá ME.
Source
Fundación Pablo Cassará, Instituto de Ciencia y TecnologÃa Dr César Milstein, Consejo Nacional de Investigaciones CientÃficas 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 (Androgenetic Alopecia), 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 Androgenetic Alopecia 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.
© 2012 The Authors. BJD © 2012 British Association of Dermatologists.
http://www.ncbi.nlm.nih.gov/pubmed/22283397
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.
Leirós GJ, Attorresi AI, Balañá ME.
Source
Fundación Pablo Cassará, Instituto de Ciencia y TecnologÃa Dr César Milstein, Consejo Nacional de Investigaciones CientÃficas 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 (Androgenetic Alopecia), 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 Androgenetic Alopecia 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.
© 2012 The Authors. BJD © 2012 British Association of Dermatologists.
http://www.ncbi.nlm.nih.gov/pubmed/22283397