title: 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.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Fundación Pablo Cassará, Instituto de Ciencia y Tecnología Dr César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad de Buenos Aires, Argentina.
authors.forename: G J
authors.initials: GJ
authors.lastname: Leirós
authors.forename: A I
authors.initials: AI
authors.lastname: Attorresi
authors.forename: M E
authors.initials: ME
authors.lastname: Balañá
mesh_terms: D000505:Alopecia / Q000473:pathology*; D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000096:biosynthesis; D020405:Dermis / Q000473:pathology; D013196:Dihydrotestosterone / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D018859:Hair Follicle / Q000473:pathology; D006801:Humans; D053564:Keratins, Hair-Specific / Q000378:metabolism; D053531:Keratins, Type II / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D012313:RNA / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000502:physiology; D012535:Scalp / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology*; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D000728:Androgens; D018076:DNA, Complementary; C502884:KRT75 protein, human; D053564:Keratins, Hair-Specific; D053531:Keratins, Type II; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D012313:RNA; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride