Strengthening the skin with topical delivery of keratinocyte growth factor-1 using a novel DNA plasmid

Chunqing Dou, Frank Lay, Amir Mehdi Ansari, Donald J. Rees, Ali Karim Ahmed, Olga Kovbasnjuk, Aerielle E. Matsangos, Junkai Du, Sayed Mohammad Hosseini, Charles Steenbergen, Karen Fox-Talbot, Aaron T. Tabor, James A. Williams, Lixin Liu, Guy P. Marti, John W. Harmon

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)752-761
Number of pages10
JournalMolecular Therapy
Volume22
Issue number4
DOIs
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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