The combination of IGF-I and KGF cDNA improves dermal and epidermal regeneration by increased VEGF expression and neovascularization

• Published in: Gene therapy Vol. 14; no. 16; pp. 1235 - 1242
• Main Authors: JESCHKE, M. G, HERNDON, D. N
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.08.2007
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; Biological and medical sciences; Biotechnology; Collagen; Collagen (type I); Collagen (type IV); Collagen Type I - metabolism; Collagen Type III - metabolism; Collagen Type IV - metabolism; Dermis - cytology; Dermis - metabolism; DNA, Complementary - administration & dosage; Epidermis - cytology; Epidermis - metabolism; Fibroblast Growth Factor 7 - genetics; Fibroblast growth factors; Fibroblast Growth Factors - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Gene therapy; Gene transfer; Genetic aspects; Genetic Therapy - methods; Health. Pharmaceutical industry; Industrial applications and implications. Economical aspects; Insulin; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-like growth factor I; Insulin-Like Growth Factor I - genetics; Insulin-like growth factors; Keratinocyte growth factor; Liposomes; Male; Medical sciences; Neovascularization; Neovascularization, Physiologic; Physical growth; Platelet-derived growth factor; Platelet-Derived Growth Factor - metabolism; Rats; Rats, Sprague-Dawley; Regeneration (Biology); Skin; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascularization; Wound Healing; United States; wound healing; growth factors; liposomes; Liposome; Gene expression; Insulin like growth factor 1; Wound; Regeneration; Vascular endothelium growth factor; Complementary DNA; Skin; Neovascularization; Gene therapy; Cicatrization; Growth factor
• DOI: 10.1038/sj.gt.3302972
• ISSN: 0969-7128

Insulin-like growth factor-I (IGF-I) and keratinocyte growth factor (KGF) cDNA gene transfer individually improves dermal and epidermal regeneration. The aim of the present study was to determine whether the combination of IGF-I plus KGF cDNA further improves wound healing and by which mechanisms these changes occur. Rats received an acute wound and were divided into four groups to receive weekly subcutaneous injections of liposomes plus Lac Z cDNA, liposomes plus IGF-I cDNA, liposomes plus KGF cDNA, or liposomes plus IGF-I/KGF cDNA. Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine IGF-I, KGF, platelet-derived growth factor, fibroblast growth factor (FGF), transforming growth factor-beta and vascular endothelial growth factor (VEGF) expression and different types of collagen (I, III and IV). IGF-I, KGF and their combination cDNA treatment significantly (P<0.05) accelerated re-epithelization, increased IGF-I, KGF, FGF, VEGF and collagen type IV expression, while it had no effect on collagen type I and III expression. The combination of IGF-I plus KGF cDNA increased (P<0.05) neovascularization and VEGF expression when compared to IGF-I cDNA, KGF cDNA groups and controls. In conclusion, exogenous administration of liposomal IGF-I plus KGF cDNA enhanced dermal and epidermal regeneration which is due to increased neovascularization.