Exogenous liposomal IGF-I cDNA gene transfer leads to endogenous cellular and physiological responses in an acute wound

Jeschke, Marc G. and Schubert, Thomas and Klein, Dagmar (2004) Exogenous liposomal IGF-I cDNA gene transfer leads to endogenous cellular and physiological responses in an acute wound. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 286 (5). R958-R966. ISSN 0363-6119

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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 mug vehicle) or liposomes plus the IGF-I cDNA (2.2 mug) and Lac Z gene (0.22 mug). 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.

Item Type: Article
Uncontrolled Keywords: KERATINOCYTE GROWTH-FACTOR; SKIN; ANGIOGENESIS; EXPRESSION; KGF; THERAPY; REPAIR; VIVO; wound healing; growth factors; gene therapy; skin
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 20 Jul 2021 08:26
Last Modified: 20 Jul 2021 08:26
URI: https://pred.uni-regensburg.de/id/eprint/37652

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