RESUMEN
Background: Skin wounds, whether medically or incidentally induced, are always at a risk of becoming infected, but the infection risks are greater when the wounds are recovering under ischemic, poorly perfused conditions. Staphylococcus aureus, which frequently infects cutaneous and soft tissue, can infect to a greater extent when wounds are poorly perfused. Bad as this may be, both MSSA and MRSA strains of S. aureus can cause severe infections, with MRSA being considered more aggressive. Methods: In this study, we used a lagomorph ear excisional wound model to initially test the influence of partial ischemia on uninfected wound healing. We then subsequently test the same ischemic injury model under an active MSSA infection and compared these wounds against normally perfused MSSA-infected wounds. Lastly, we test whether differences in healing exist between MSSA-infected and MRSA-infected wounds, both under the same ischemic model. Results: The data suggest that partial ischemia considerably reduces healing of noninfected wounds (epithelial gap P=∗∗∗∗, granulation gap P=∗∗∗, and granulation area P=∗∗∗∗). Similarly, partial ischemic wounds coupled with MSSA infection display healing impairments against likewise-infected wounds healing under normal perfusion (epithelial gap P=∗, granulation gap P=∗, and granulation area P=∗∗). No significant differences were observed between MSSA-infected and MRSA-infected wounds healing under ischemia. Conclusion: The data produced quantitative differences in healing under various conditions consequent to ischemia and S. aureus infection. Although it is well recognized that ischemia and infection adversely influence healing, by testing these conditions, we determined the detrimental magnitude such circumstances inflict on skin healing, thereby providing a relative reference to compare and gauge when met with similar conditions clinically.
RESUMEN
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.
RESUMEN
Fibrotic skin conditions, such as hypertrophic and keloid scars, frequently result from injury to the skin and as sequelae to surgical procedures. The development of skin fibrosis may lead to patient discomfort, limitation in range of motion, and cosmetic disfigurement. Despite the frequency of skin fibrosis, treatments that seek to address the root causes of fibrosis are lacking. Much research into fibrotic pathophysiology has focused on dermal pathology, but less research has been performed to understand aberrations in fibrotic epidermis, leading to an incomplete understanding of dermal fibrosis. Herein, literature on occlusion, a treatment modality known to reduce dermal fibrosis, in part through accelerating wound healing and regulating aberrant epidermal inflammation that otherwise drives fibrosis in the dermis, is reviewed. The review focuses on epidermal-dermal crosstalk, which contributes to the development and maintenance of dermal fibrosis, an underemphasized interplay that may yield novel strategies for treatment if understood in more detail.