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Mol Ther ; 22(4): 752-61, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24434934

RESUMO

Fragile skin, susceptible to decubitus ulcers and incidental trauma, is a problem particularly for the elderly and for those with spinal cord injury. Here, we present a simple approach to strengthen the skin by the topical delivery of keratinocyte growth factor-1 (KGF-1) DNA. In initial feasibility studies with the novel minimalized, antibiotic-free DNA expression vector, NTC8385-VA1, the reporter genes luciferase and enhanced green fluorescent protein were delivered. Transfection was documented when luciferase expression significantly increased after transfection. Microscopic imaging of enhanced green fluorescent protein-transfected skin showed green fluorescence in hair follicles, hair shafts, and dermal and superficial epithelial cells. With KGF-1 transfection, KGF-1 mRNA level and protein production were documented with quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Epithelial thickness of the transfected skin in the KGF group was significantly increased compared with the control vector group (26 ± 2 versus 16 ± 4 µm) at 48 hours (P = 0.045). Dermal thickness tended to be increased in the KGF group (255 ± 36 versus 162 ± 16 µm) at 120 hours (P = 0.057). Biomechanical assessment showed that the KGF-1-treated skin was significantly stronger than control vector-transfected skin. These findings indicate that topically delivered KGF-1 DNA plasmid can increase epithelial thickness and strength, demonstrating the potential of this approach to restore compromised skin.


Assuntos
Fator 7 de Crescimento de Fibroblastos/genética , Técnicas de Transferência de Genes , Terapia Genética , Anormalidades da Pele/genética , Administração Tópica , Animais , DNA/administração & dosagem , DNA/genética , Fator 7 de Crescimento de Fibroblastos/administração & dosagem , Humanos , Camundongos , Plasmídeos/administração & dosagem , Anormalidades da Pele/terapia , Cicatrização/genética
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