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The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells

Activation of Wnt/β-catenin signaling in adult mouse epidermis leads to expansion of the stem cell compartment and redirects keratinocytes in the interfollicular epidermis and sebaceous glands (SGs) to differentiate along the hair follicle (HF) lineages. Here we demonstrate that during epidermal dev...

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Detalles Bibliográficos
Autores principales: Kretzschmar, Kai, Cottle, Denny L, Schweiger, Pawel J, Watt, Fiona M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641324/
https://www.ncbi.nlm.nih.gov/pubmed/26121213
http://dx.doi.org/10.1038/jid.2015.242
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author Kretzschmar, Kai
Cottle, Denny L
Schweiger, Pawel J
Watt, Fiona M
author_facet Kretzschmar, Kai
Cottle, Denny L
Schweiger, Pawel J
Watt, Fiona M
author_sort Kretzschmar, Kai
collection PubMed
description Activation of Wnt/β-catenin signaling in adult mouse epidermis leads to expansion of the stem cell compartment and redirects keratinocytes in the interfollicular epidermis and sebaceous glands (SGs) to differentiate along the hair follicle (HF) lineages. Here we demonstrate that during epidermal development and homeostasis there is reciprocal activation of the androgen receptor (AR) and β-catenin in cells of the HF bulb. AR activation reduced β-catenin-dependent transcription, blocked β-catenin-induced induction of HF growth, and prevented β-catenin-mediated conversion of SGs into HFs. Conversely, AR inhibition enhanced the effects of β-catenin activation, promoting HF proliferation and differentiation, culminating in the formation of benign HF tumors and a complete loss of SG identity. We conclude that AR signaling has a key role in epidermal stem cell fate selection by modulating responses to β-catenin in adult mouse skin.
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spelling pubmed-46413242015-12-04 The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells Kretzschmar, Kai Cottle, Denny L Schweiger, Pawel J Watt, Fiona M J Invest Dermatol Original Article Activation of Wnt/β-catenin signaling in adult mouse epidermis leads to expansion of the stem cell compartment and redirects keratinocytes in the interfollicular epidermis and sebaceous glands (SGs) to differentiate along the hair follicle (HF) lineages. Here we demonstrate that during epidermal development and homeostasis there is reciprocal activation of the androgen receptor (AR) and β-catenin in cells of the HF bulb. AR activation reduced β-catenin-dependent transcription, blocked β-catenin-induced induction of HF growth, and prevented β-catenin-mediated conversion of SGs into HFs. Conversely, AR inhibition enhanced the effects of β-catenin activation, promoting HF proliferation and differentiation, culminating in the formation of benign HF tumors and a complete loss of SG identity. We conclude that AR signaling has a key role in epidermal stem cell fate selection by modulating responses to β-catenin in adult mouse skin. Nature Publishing Group 2015-11 2015-07-16 /pmc/articles/PMC4641324/ /pubmed/26121213 http://dx.doi.org/10.1038/jid.2015.242 Text en Copyright © 2015 The Society for Investigative Dermatology, Inc http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Article
Kretzschmar, Kai
Cottle, Denny L
Schweiger, Pawel J
Watt, Fiona M
The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells
title The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells
title_full The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells
title_fullStr The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells
title_full_unstemmed The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells
title_short The Androgen Receptor Antagonizes Wnt/β-Catenin Signaling in Epidermal Stem Cells
title_sort androgen receptor antagonizes wnt/β-catenin signaling in epidermal stem cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4641324/
https://www.ncbi.nlm.nih.gov/pubmed/26121213
http://dx.doi.org/10.1038/jid.2015.242
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