title: Strengthening the skin with topical delivery of keratinocyte growth factor-1 using a novel DNA plasmid.
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.
authors.affiliation: 1] Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China [2] Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Chunqing
authors.initials: C
authors.lastname: Dou
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Lay
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Amir Mehdi
authors.initials: AM
authors.lastname: Ansari
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Rees
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ali Karim
authors.initials: AK
authors.lastname: Ahmed
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Kovbasnjuk
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Aerielle E
authors.initials: AE
authors.lastname: Matsangos
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Junkai
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Sayed Mohammad
authors.initials: SM
authors.lastname: Hosseini
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Steenbergen
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Fox-Talbot
authors.affiliation: GenArmor, Winston Salem, North Carolina, USA.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Tabor
authors.affiliation: Nature Technology Corporation, Lincoln, Nebraska, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Williams
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Guy P
authors.initials: GP
authors.lastname: Marti
authors.affiliation: Department of Surgery and Hendrix Burn/Wound Laboratory, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Harmon
mesh_terms: D000287:Administration, Topical; D000818:Animals; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D010957:Plasmids / Q000008:administration & dosage; D012868:Skin Abnormalities / Q000235:genetics* / Q000628:therapy; D014945:Wound Healing / Q000235:genetics
chemical_list: D051523:Fibroblast Growth Factor 7; D004247:DNA