β-catenin stabilization in skin fibroblasts causes fibrotic lesions by preventing adipocyte differentiation of the reticular dermis

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Abstract

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.

Original languageEnglish
JournalJournal of Investigative Dermatology
Early online date19 Feb 2016
DOIs
Publication statusE-pub ahead of print - 19 Feb 2016

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