TY - JOUR
T1 - β-catenin stabilization in skin fibroblasts causes fibrotic lesions by preventing adipocyte differentiation of the reticular dermis
AU - Mastrogiannaki, Maria
AU - Lichtenberger, Beate M
AU - Reimer, Andreas
AU - Collins, Charlotte A
AU - Driskell, Ryan R
AU - Watt, Fiona M
N1 - Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2016/2/19
Y1 - 2016/2/19
N2 - The Wnt/β-catenin pathway plays a central role in epidermal homeostasis and regeneration but how it affects fibroblast fate decisions is unknown. Here, we investigated the effect of targeted β-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of Sca1- and Sca1+ neonatal fibroblasts, from upper and lower dermis respectively, confirmed that Sca1+ cells had a pre-adipocyte signature and revealed 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 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.
AB - The Wnt/β-catenin pathway plays a central role in epidermal homeostasis and regeneration but how it affects fibroblast fate decisions is unknown. Here, we investigated the effect of targeted β-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of Sca1- and Sca1+ neonatal fibroblasts, from upper and lower dermis respectively, confirmed that Sca1+ cells had a pre-adipocyte signature and revealed 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 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.
U2 - 10.1016/j.jid.2016.01.036
DO - 10.1016/j.jid.2016.01.036
M3 - Article
C2 - 26902921
SN - 0022-202X
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
ER -