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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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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. |
format | Online Article Text |
id | pubmed-4641324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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