Exogenous liposomal IGF-I cDNA gene transfer leads to endogenous cellular and physiological responses in an acute wound.
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.
Jeschke
Marc G
MG
Klinik für Chirurgie, Abteilung für Plastische und Handchirurgie, Friedrich-Alexander University Erlangen, Krankenhausstrasse 12, 91054 Erlangen, Germany. Mcjeschke@hotmail.com
Schubert
Thomas
T
Klein
Dagmar
D
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*
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