title: Gene expression profiling of negative-pressure-treated skin graft donor site wounds.
abstract: Negative-pressure wound therapy (NPWT) is widely used to improve skin wound healing. Although NPWT has been studied as a treatment for wound closure and healing, the molecular mechanisms explaining its therapeutic effects remain unclear. To investigate the effect of NPWT on gene expression, and to discover the genes most dominantly responding to this treatment during skin wound healing, we applied negative pressure on split-thickness skin graft donor sites from the first postoperative day (POD) to the seventh POD. Biopsies were collected from 4 NPWT-treated and 2 control patients. Two biopsy samples were taken from each patient: one from intact skin before graft harvesting, and one on the seventh POD from the donor site wound. Genome-wide microarrays were performed on all samples. Gene expression changes on the seventh POD were compared between NPWT and control patients, and were analyzed for statistical significance. In addition, we analyzed wound exudates for volume, and for concentrations of leukocytes, erythrocytes, and haemoglobin. NPWT induced major changes in gene expression during healing. These changes ranged from 10-fold induction to 27-fold suppression. The genes most induced were associated with cell proliferation and inflammation, and the most down-regulated genes were linked to epidermal differentiation. Our results provide the first insight into the molecular mechanisms behind NPWT, and suggest that NPWT enhances specific inflammatory gene expression at the acute phase associated with epithelial migration and wound healing. However, its continued use may inhibit epithelial differentiation.
authors.affiliation: Institute of Biomedicine, Pharmacology, Biomedicum, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland. kristo.nuutila@helsinki.fi
authors.forename: Kristo
authors.initials: K
authors.lastname: Nuutila
authors.forename: Antti
authors.initials: A
authors.lastname: Siltanen
authors.forename: Matti
authors.initials: M
authors.lastname: Peura
authors.forename: Ari
authors.initials: A
authors.lastname: Harjula
authors.forename: Tapio
authors.initials: T
authors.lastname: Nieminen
authors.forename: Jyrki
authors.initials: J
authors.lastname: Vuola
authors.forename: Esko
authors.initials: E
authors.lastname: Kankuri
authors.forename: Pertti
authors.initials: P
authors.lastname: Aarnio
mesh_terms: D000328:Adult; D000368:Aged; D004912:Erythrocytes / Q000166:cytology; D005122:Exudates and Transudates / Q000166:cytology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D054843:Negative-Pressure Wound Therapy; D060053:Transplant Donor Site / Q000502:physiology* / Q000601:surgery; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000235:genetics / Q000378:metabolism*
chemical_list: D006454:Hemoglobins