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Hair follicle stem cell differentiation is inhibited through a cross talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia.
MedLine Citation:
PMID:  22283397     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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/ß-catenin signaling is known to positively affect mammalian hair growth. In androgenetic alopecia (AGA) androgens cause HF miniaturization through a mechanism which 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 co-culture model with DPC or culturing them with media conditioned by DPC after activation of androgen and Wnt/ß-catenin signalling pathways. To study the molecular cross talk between androgen and Wnt signalling pathway in DPC, we analyzed the expression and activation of downstream Wnt signalling molecules in the presence of androgens. Results:  In a co-culture model with human DPC from patients suffering AGA and HF stem cells, we observed that androgens abrogate hair differentiation evaluated by hair-specific keratin 6 (K6hf) expression. Wnt signaling 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 up-regulation 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.
Authors:
G J Leirós; A I Attorresi; M E Balañá
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-27
Journal Detail:
Title:  The British journal of dermatology     Volume:  -     ISSN:  1365-2133     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0004041     Medline TA:  Br J Dermatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 British Association of Dermatologists.
Affiliation:
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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