title: Exogenous liposomal IGF-I cDNA gene transfer leads to endogenous cellular and physiological responses in an acute wound.
abstract: The purpose of the present study was to examine whether exogenous liposomal cDNA gene transfer is recognized by the cell and causes endogenous cellular and physiological responses. When administered as a protein, IGF-I is known to cause adverse side effects due to lack of cellular responses. Therefore, we used IGF-I cDNA as a vector to study cellular and physiological effects after liposomal administration to wounded skin. Sprague-Dawley rats were given a scald burn to inflict an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.2 microg vehicle) or liposomes plus the IGF-I cDNA (2.2 microg) and Lac Z gene (0.22 microg). Transfection was confirmed by histochemical assays for beta-galactosidase. Planimetry, immunological assays, and histological and immunohistochemical techniques were used to determine molecular mechanisms after gene transfer, protein expression, and dermal and epidermal regeneration. IGF-I cDNA transfer increased IGF-I protein expression and caused concomitant cellular responses by increasing IGF binding protein (IGFBP)-3 and decreasing IGFBP-1. IGF-I cDNA gene transfer increased keratinocyte growth factor expression and exerted promitogenic antiapoptotic effects on basal keratinocytes, thus improving epidermal regeneration. IGF-I cDNA improved dermal regeneration by an increased collagen deposition and morphology. IGF-I cDNA increased VEGF concentrations and thus neovascularization. Exogenous-administered IGF-I cDNA is recognized by the cell and leads to similar intracellular responses as the endogenous gene. Liposomal IGF-I gene transfer further leads to improved dermal and epidermal regeneration by interacting with other growth factors.
authors.affiliation: Klinik für Chirurgie, Abteilung für Plastische und Handchirurgie, Friedrich-Alexander University Erlangen, Krankenhausstrasse 12, 91054 Erlangen, Germany. Mcjeschke@hotmail.com
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
authors.forename: Thomas
authors.initials: T
authors.lastname: Schubert
authors.forename: Dagmar
authors.initials: D
authors.lastname: Klein
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D020405:Dermis / Q000098:blood supply / Q000293:injuries / Q000502:physiology; D004817:Epidermis / Q000293:injuries* / Q000502:physiology*; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000378:metabolism; D015316:Genetic Therapy; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D054835:Lipocalin 1; D008081:Liposomes; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection / Q000379:methods*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; C496455:Fgf7 protein, rat; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; C518449:Lcn1 protein, rat; D054835:Lipocalin 1; D008081:Liposomes; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D003094:Collagen