Liposomal gene transfer of keratinocyte growth factor improves wound healing by altering growth factor and collagen expression.
BACKGROUND
Growth factors affect the complex cascade of wound healing; however, interaction between different growth factors during dermal and epidermal regeneration are still not entirely defined. In the present study, we thought to determine the interaction between keratinocyte growth factor (KGF) administered as liposomal cDNA with other dermal and epidermal growth factors and collagen synthesis in an acute wound.


METHODS
Rats received an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.22 microg, vehicle), or liposomes plus the KGF cDNA (2.2 microg) and Lac-Z gene (0.22 microg). Histological and immunohistochemical techniques were used to determine growth factor, collagen expression, and dermal and epidermal structure.


RESULTS
KGF cDNA increased insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and fibroblast growth factor (FGF), decreased transforming growth factor-beta (TGF-beta), while it had no effect on platelet-derived growth factor (PDGF) levels in the wound. KGF cDNA significantly increased collagen Type IV at both the wound edge as well as the wound bed, while it had no effect on collagen Type I and III. KGF cDNA increased re-epithelialization, improved dermal regeneration, and increased neovascularization.


CONCLUSIONS
Exogenous administered KGF cDNA causes increases in IGF-I, IGF-BP3, FGF, and collagen IV and decreases TGF-beta concentration. KGF gene transfer accelerates wound healing without causing an increase in collagen I or III.
Pereira
Clifford T
CT
Shriners Hospitals for Children, University of Texas Medical Branch, Galveston, Texas 77550, USA.
Herndon
David N
DN
Rocker
Roland
R
Jeschke
Marc G
MG
D000818:Animals; D002056:Burns / Q000378:metabolism / Q000503:physiopathology*; D003094:Collagen / Q000378:metabolism*; D024141:Collagen Type IV / Q000378:metabolism; D004848:Epithelium / Q000503:physiopathology; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage* / Q000235:genetics* / Q000494:pharmacology; D018014:Gene Transfer Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008081:Liposomes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects*
D024141:Collagen Type IV; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D051523:Fibroblast Growth Factor 7; D003094:Collagen