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Updated: Jun 16, 2025
Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
Published on: March 24, 2017
Skin fibrosis is accompanied by increased expression of secreted frizzled-related protein-2
David M Dolivo1, Adrian E Rodrigues1, Lauren S Sun1
1Department of Surgery, Northwestern University-The Feinberg School of Medicine, Chicago, Illinois, USA.
Abstract:
Dermal fibrosis is a consequence of damage to skin and is accompanied by dysfunction and cosmetic disfigurement. Improved understanding of the pathological factors driving skin fibrosis is critical to development of therapeutic modalities. Here, we describe that the Wnt signalling antagonist SFRP2 is upregulated in organotypic keratinocyte cultures upon experimental reduced hydration, a model that simulates the aberrant epidermal barrier state characteristic of several skin pathologies, including those that manifest in development of fibrosis. Consistent with this, we find that SFRP2 is overexpressed in both the dermis and epidermis of human hypertrophic scar tissue and lesional tissue of a mouse scleroderma model. Knockdown of SFRP2 expression in human fibroblasts antagonises proliferation and myofibroblast differentiation, including deposition of type I collagen, suggesting that SFRP2 signalling in fibroblasts may contribute to propagation of fibrosis in hypertrophic scar, as well as in other clinical indications characterised by skin fibrosis.
Insights
Secreted frizzled-related protein 2 (SFRP2) is upregulated in skin fibrosis. Reducing SFRP2 in fibroblasts inhibits key fibrotic processes, suggesting SFRP2 as a therapeutic target for skin scarring and related conditions.
Area of Science:
- Dermatology
- Fibrosis Research
- Molecular Biology
Background:
- Dermal fibrosis, a common skin condition, results from skin damage and leads to dysfunction and cosmetic issues.
- Understanding the molecular drivers of skin fibrosis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of the Wnt signaling antagonist SFRP2 in dermal fibrosis.
- To determine if SFRP2 is a potential therapeutic target for fibrotic skin diseases.
Main Methods:
- Organotypic keratinocyte cultures were used to model reduced hydration, mimicking aberrant epidermal barrier states.
- SFRP2 expression was analyzed in human hypertrophic scar tissue and a mouse scleroderma model.
- SFRP2 knockdown was performed in human fibroblasts to assess its impact on proliferation and myofibroblast differentiation.
Main Results:
- SFRP2 was found to be upregulated in keratinocyte cultures with reduced hydration.
- Overexpression of SFRP2 was observed in both the dermis and epidermis of human hypertrophic scars and in mouse scleroderma lesions.
- Knockdown of SFRP2 in human fibroblasts reduced proliferation, myofibroblast differentiation, and type I collagen deposition.
Conclusions:
- SFRP2 plays a significant role in the pathogenesis of skin fibrosis.
- SFRP2 signaling in fibroblasts contributes to the progression of hypertrophic scarring and other fibrotic skin conditions.
- SFRP2 represents a potential therapeutic target for treating dermal fibrosis.
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