In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair.

Andree, Christoph; Swain, William F.; Page, Curtis P.; Macklin, Michael D.; Sláma, Jaromír; Hatzis, Dimitrios; Eriksson, Elof

doi:10.1073/pnas.91.25.12188

Cited by 191 publications

(120 citation statements)

References 34 publications

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“…But the gene gun results in highly variable gene expression. [12][13][14] Although virally mediated gene delivery has high transfection efficiency there are serious concerns about its safety and potential pathogenicity. 15 Our laboratory has been investigating the possibility of using naked DNA injection coupled with electroporation.…”

Section: Introductionmentioning

confidence: 99%

Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model

et al. 2004

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We recently demonstrated that electroporation enhances transfection in a mouse wound-healing model. Keratinocyte growth factor (KGF) is an inducer of epithelial cell proliferation and differentiation and has been shown to be under expressed in the wounds of diabetic individuals. We hypothesized that KGF delivered into an excisional wound via naked DNA injection with subsequent electroporation would be a novel and potentially effective method to enhance wound closure in a diabetic mouse model. ELISA assays confirmed production of KGF protein in cultured mouse cells and RT-PCR assays confirmed KGF mRNA in skin samples taken from mice. In all, 32 genetically diabetic mice were given two identical excisional wounds of their dorsum and split into two groups with one group receiving KGF DNA injection and electroporation with the other group receiving no treatment. Over 90% of wounds healed in the presence of KGF and electroporation versus 40% in the untreated group by day 12. Histological analysis of the wounds demonstrated that untreated wounds contained microulcers with thin or incomplete epithelium with unresolved inflammation as compared to treated wounds where intact and mature epithelium was observed. Taken together these findings suggest that a single injection of KGF DNA encoded on a plasmid coupled with electroporation improves and accelerates wound closure in a delayed wound-healing model.

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Section: Introductionmentioning

confidence: 99%

Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model

et al. 2004

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“…There are also common pathways, such as the extracellular regulated kinase (ERK) pathway of MAP kinases, which transduce signals upon activation of both EGF and FGF receptors (Karin et al, 1997). Furthermore, EGF and FGF-2 are able to promote regeneration processes, such as wound healing (Andree et al, 1994;Brown et al, 1989;Davidson and Broadley, 1991). It is remarkable that although sharing all these activities, the gene expression pattern the growth factors induce in one cell type is only partially overlapping.…”

Section: Introductionmentioning

confidence: 99%

The activation and composition of FiRE (an FGF-inducible response element) differ in a cell type- and growth factor-specific manner

1998

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The expression of the heparan sulfate proteoglycan, syndecan-1, is induced both in keratinocytes and in ®broblasts during development and tissue regeneration. Here we report that in keratinocytes the syndecan-1 gene was stimulated by EGF but not by FGF-2. In ®broblasts it was stimulated by FGF-2 but not by EGF. Likewise, the recently discovered FGF-inducible response element (FiRE) on the gene of syndecan-1 was stimulated by FGF-2 in ®broblasts and by EGF in keratinocytes, but not vice versa. The FiRE has two binding sites for an activator protein-1 (AP-1), one for an FGF-inducible nuclear factor (FIN-1) and one for an upstream stimulatory factor-1 (USF-1). The growth factorstimulated binding of these transcription factors, as well as their requirement for FiRE activation, varied between the two cell types. First, although AP-1s were required for activation of FiRE in both cell types, the binding of AP-1 to FiRE was increased by growth factor-stimulation only in ®broblasts and not in keratinocytes. Secondly, FiRE did not bind FIN-1 nor needed the FIN-1 binding site for EGF-stimulated activation in keratinocytes, in contrast to the FGF-stimulated activation of FiRE in ®broblasts. Thirdly, EGF, which did not activate FiRE in ®broblasts, failed to activate FIN-1 in these cells. Finally, an USF-1 binding site that was necessary for activation of FiRE in keratinocytes was not needed in ®broblasts. These data suggest mechanisms by which members of the EGF-and FGF-families can di erentially stimulate transcription through AP-1 regulated elements in a cell type-speci®c manner.

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“…Skin-directed gene transfer might be used for the treatment of a variety of skin diseases, [4][5][6][7][8] including acquired disorders such as cancer, burns or chronic non-healing wounds, [9][10][11] or inherited diseases such as epidermolysis bullosa, ichthyosis and xeroderma pigmentosum. [12][13][14][15][16] Moreover, systemic diseases such as adenosine deaminase deficiency, hemophilia A or B, and renal anemia might also be treated by transfer of a relevant therapeutic gene into the skin.…”

mentioning

confidence: 99%

Efficient gene transfer into human keratinocytes with recombinant adeno-associated virus vectors

Braun‐Falco

Doenecke

Smola³

et al. 1999

Gene Ther

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Gene transfer into the skin is a promising approach to treat duced within 48 h. This effect was independent of individinherited or acquired dermatological diseases and sysual skin donors and different body areas serving as the temic monogenic deficiencies. For this purpose, the source for keratinocyte isolation. rAAV had no significant efficient and sustained gene delivery into keratinocytes is influence on cell viability, but induced a growth arrest in of critical importance. Recombinant adeno-associated transduced keratinocytes. This growth arrest was overvirus (rAAV) vectors hold the potential to achieve a longcome by replating cells in fresh media. rAAV/GFP-transterm gene transfer into various human organs. In order to duced keratinocytes could be passaged several times, evaluate this potential for skin gene therapy, human keraexpressed GFP for up to 50 days, and passed the transtinocytes were transduced in vitro with rAAV vectors encogene to their daughter cells, suggesting that keratinocyte ding the reporter genes ␤-galactosidase (rAAV/LacZ) or precursor cells were also transduced. Taken together, the green fluorescent protein (rAAV/GFP). Using rAAV/LacZ at results suggest that rAAV is a promising gene transfer a multiplicity of infection (MOI) of five transducing particles vehicle for skin gene therapy. per cell, up to 70% of human keratinocytes were trans-

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In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair.

Cited by 191 publications

References 34 publications

Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model

Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model

The activation and composition of FiRE (an FGF-inducible response element) differ in a cell type- and growth factor-specific manner

Efficient gene transfer into human keratinocytes with recombinant adeno-associated virus vectors

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