β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis

The Wnt/β-catenin pathway plays a central role in epidermal homeostasis and regeneration, but how it affects fibroblast fate decisions is unknown. We investigated the effect of targeted β-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of stem cell antigen 1- (Sca1...

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Main Authors:	Mastrogiannaki, Maria, Lichtenberger, Beate M., Reimer, Andreas, Collins, Charlotte A., Driskell, Ryan R., Watt, Fiona M.
Format:	Online
Language:	English
Published:	Elsevier 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874948/

id	pubmed-4874948
recordtype	oai_dc
spelling	pubmed-48749482016-06-01 β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis Mastrogiannaki, Maria Lichtenberger, Beate M. Reimer, Andreas Collins, Charlotte A. Driskell, Ryan R. Watt, Fiona M. Original Article The Wnt/β-catenin pathway plays a central role in epidermal homeostasis and regeneration, but how it affects fibroblast fate decisions is unknown. We investigated the effect of targeted β-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of stem cell antigen 1- (Sca1-) and Sca1+ neonatal fibroblasts from upper and lower dermis, respectively, confirmed that Sca1+ cells had a preadipocyte signature and showed differential expression of Wnt/β-catenin–associated genes. By targeting all fibroblasts or selectively targeting Dlk1+ lower dermal fibroblasts, we found that β-catenin stabilization between developmental stages E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1+ fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/β-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases. Elsevier 2016-06 /pmc/articles/PMC4874948/ /pubmed/26902921 http://dx.doi.org/10.1016/j.jid.2016.01.036 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mastrogiannaki, Maria Lichtenberger, Beate M. Reimer, Andreas Collins, Charlotte A. Driskell, Ryan R. Watt, Fiona M.
spellingShingle	Mastrogiannaki, Maria Lichtenberger, Beate M. Reimer, Andreas Collins, Charlotte A. Driskell, Ryan R. Watt, Fiona M. β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis
author_facet	Mastrogiannaki, Maria Lichtenberger, Beate M. Reimer, Andreas Collins, Charlotte A. Driskell, Ryan R. Watt, Fiona M.
author_sort	Mastrogiannaki, Maria
title	β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis
title_short	β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis
title_full	β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis
title_fullStr	β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis
title_full_unstemmed	β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis
title_sort	β-catenin stabilization in skin fibroblasts causes fibrotic lesions by preventing adipocyte differentiation of the reticular dermis
description	The Wnt/β-catenin pathway plays a central role in epidermal homeostasis and regeneration, but how it affects fibroblast fate decisions is unknown. We investigated the effect of targeted β-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of stem cell antigen 1- (Sca1-) and Sca1+ neonatal fibroblasts from upper and lower dermis, respectively, confirmed that Sca1+ cells had a preadipocyte signature and showed differential expression of Wnt/β-catenin–associated genes. By targeting all fibroblasts or selectively targeting Dlk1+ lower dermal fibroblasts, we found that β-catenin stabilization between developmental stages E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1+ fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/β-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases.
publisher	Elsevier
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874948/
_version_	1613582315882020864

β-Catenin Stabilization in Skin Fibroblasts Causes Fibrotic Lesions by Preventing Adipocyte Differentiation of the Reticular Dermis

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