HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Jeschke, M. G. Articles by Klein, D. Search for Related Content PubMed PubMed Citation Articles by Jeschke, M. G. Articles by Klein, D.

INFLAMMATION, CYTOKINES, AND TEMPERATURE REGULATION

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

¹Department of Surgery, Friedrich-Alexander University Erlangen, 91054 Erlangen; and ²Institute of Pathology, University Regensburg, Regensburg, Germany

Submitted 22 September 2003 ; accepted in final form 29 December 2003

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 µg vehicle) or liposomes plus the IGF-I cDNA (2.2 µg) and Lac Z gene (0.22 µg). Transfection was confirmed by histochemical assays for -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.

wound healing; growth factors; gene therapy; skin

This article has been cited by other articles:

				E. Semenova, H. Koegel, S. Hasse, J. E. Klatte, E. Slonimsky, D. Bilbao, R. Paus, S. Werner, and N. Rosenthal Overexpression of mIGF-1 in Keratinocytes Improves Wound Healing and Accelerates Hair Follicle Formation and Cycling in Mice Am. J. Pathol., November 1, 2008; 173(5): 1295 - 1310. [Abstract] [Full Text] [PDF]