Abstract
Wound healing is significantly delayed in irradiated skin. To better understand global changes in protein expression after radiation, we utilized a reverse phase protein array (RPPA) to identify significant changes in paired samples of normal and irradiated human skin. Of the 210 proteins studied, fibronectin was the most significantly and consistently downregulated in radiation-damaged skin. Using a murine model, we confirmed that radiation leads to decreased fibronectin expression in the skin as well as delayed wound healing. Topically applied fibronectin was found to significantly improve wound healing in irradiated skin and was associated with decreased inflammatory infiltrate and increased angiogenesis. Fibronectin treatment may be a useful adjunctive modality in the treatment of non-healing radiation wounds.
Highlights
Radiation therapy is an important part of the treatment of solid tumors, it has dose-limiting ill effects on normal tissues
To date there has been no evaluation of fibronectin levels in human skin that has been irradiated in vivo
Topical fibronectin gel led to significantly improved healing in irradiated wounds. This was associated with a significant reduction in acute inflammation and an increase in angiogenesis. These findings suggest that fibronectin may be involved in the pathogenesis of poor wound healing after radiation skin injury, and that exogenous supplementation may assist in the repair of radiation-damaged tissue
Summary
Radiation therapy is an important part of the treatment of solid tumors, it has dose-limiting ill effects on normal tissues. Fibroblasts, which comprise a crucial role in the remodeling phase of collagen deposition and remodeling, produce highly disorganized collagen framework leading to impaired wound strength[7, 8] The culmination of these negative effects of radiation on wound healing manifests clinically as atrophic, dry, dyspigmented skin that is commonly fibrotic and/or ulcerated, healing poorly or not at all[9]. This was associated with a significant reduction in acute inflammation and an increase in angiogenesis These findings suggest that fibronectin may be involved in the pathogenesis of poor wound healing after radiation skin injury, and that exogenous supplementation may assist in the repair of radiation-damaged tissue
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