024 NonViral Gene Transfer of Keratinocyte Growth Factor in a Murine Wound

Abstract

Introduction: Growth factors have been shown to affect the complex cascade of wound healing; however, interaction between different growth factors during dermal and epidermal regeneration are still not entirely defined. In the present study we determined the interaction between keratinocyte growth factor (KGF), an epidermal growth factor, administered as liposomal cDNA, with other dermal and epidermal growth factors and collagen types I, III, and IV synthesis in an acute wound. Method: Adult male Sprague-Dawley rats received 30% total body surface area scalds under general anesthesia. They were then divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac Z gene (0.2 μg, vehicle), or liposomes plus the KGF cDNA (2.2 μg) and Lac Z gene (0.2 μg), for 4 weeks. Immunological assays, histological, and immunohistochemical techniques were used to determine growth factor concentrations and different types of collagen (I, III, and IV), rate of reepithelialization and dermal morphology, after KGF cDNA gene transfer. Results: KGF cDNA transfer significantly increased IGF-I (Insulin-like Growth Factor-I), IGFBP-3 (Insulin-like Growth Factor Binding Protein-3), and FGF (Fibroblast Growth Factor) and decreased TGF-β(Transforming Growth Factor–beta) levels (p < 0.05). KGF had no effect on PDGF (Platelet-Derived Growth Factor). KGF cDNA significantly increased collagen type IV (p < 0.02) at the wound edge as well as the wound bed, while it had no effect on collagen type I and III. KGF cDNA significantly increased reepithelialization compared to the control group. Conclusion: Exogenous KGF cDNA increases IGF-I, IGF-BP3, FGF expression and decreases TGF-β concentration in an acute wound. It accelerates re-epithelialization, improves dermal morphology and increases basement membrane formation, without a concomitant increase in inflammation or scarring. Acknowledgments: Clayton Foundation for Research

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