PMID- 22283397
OWN - NLM
STAT- MEDLINE
DCOM- 20120709
LR  - 20220408
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 166
IP  - 5
DP  - 2012 May
TI  - Hair follicle stem cell differentiation is inhibited through cross-talk between 
      Wnt/beta-catenin and androgen signalling in dermal papilla cells from patients with 
      androgenetic alopecia.
PG  - 1035-42
LID - 10.1111/j.1365-2133.2012.10856.x [doi]
AB  - 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/beta-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/beta-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 beta-catenin protein ratio and upregulation of the activity of 
      glycogen synthase kinase-3beta 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.
CI  - (c) 2012 The Authors. BJD (c) 2012 British Association of Dermatologists.
FAU - Leiros, G J
AU  - Leiros GJ
AD  - Fundacion Pablo Cassara, Instituto de Ciencia y Tecnologia Dr Cesar Milstein, 
      Consejo Nacional de Investigaciones Cientificas y Tecnicas, Ciudad de Buenos 
      Aires, Argentina.
FAU - Attorresi, A I
AU  - Attorresi AI
FAU - Balana, M E
AU  - Balana ME
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Androgens)
RN  - 0 (DNA, Complementary)
RN  - 0 (KRT75 protein, human)
RN  - 0 (Keratins, Hair-Specific)
RN  - 0 (Keratins, Type II)
RN  - 0 (Receptors, Androgen)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - G4962QA067 (Lithium Chloride)
SB  - IM
MH  - Alopecia/*pathology
MH  - Androgens/pharmacology/*physiology
MH  - Cell Differentiation/*physiology
MH  - Cells, Cultured
MH  - DNA, Complementary/biosynthesis
MH  - Dermis/pathology
MH  - Dihydrotestosterone/pharmacology
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hair Follicle/pathology
MH  - Humans
MH  - Keratins, Hair-Specific/metabolism
MH  - Keratins, Type II/metabolism
MH  - Lithium Chloride/pharmacology
MH  - Male
MH  - RNA/isolation & purification
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Androgen/physiology
MH  - Scalp/metabolism
MH  - Stem Cells/*pathology
MH  - Transfection
MH  - Wnt Signaling Pathway/*physiology
EDAT- 2012/01/31 06:00
MHDA- 2012/07/10 06:00
CRDT- 2012/01/31 06:00
PHST- 2012/01/31 06:00 [entrez]
PHST- 2012/01/31 06:00 [pubmed]
PHST- 2012/07/10 06:00 [medline]
AID - 10.1111/j.1365-2133.2012.10856.x [doi]
PST - ppublish
SO  - Br J Dermatol. 2012 May;166(5):1035-42. doi: 10.1111/j.1365-2133.2012.10856.x.