Gene expression profiling of cutaneous wound healing.
BACKGROUND
Although the sequence of events leading to wound repair has been described at the cellular and, to a limited extent, at the protein level this process has yet to be fully elucidated. Genome wide transcriptional analysis tools promise to further define the global picture of this complex progression of events.


METHODS
This study was part of a placebo-controlled double-blind clinical trial in which basal cell carcinomas were treated topically with an immunomodifier--toll-like receptor 7 agonist: imiquimod. The fourteen patients with basal cell carcinoma in the placebo arm of the trial received placebo treatment consisting solely of vehicle cream. A skin punch biopsy was obtained immediately before treatment and at the end of the placebo treatment (after 2, 4 or 8 days). 17.5K cDNA microarrays were utilized to profile the biopsy material.


RESULTS
Four gene signatures whose expression changed relative to baseline (before wound induction by the pre-treatment biopsy) were identified. The largest group was comprised predominantly of inflammatory genes whose expression was increased throughout the study. Two additional signatures were observed which included preferentially pro-inflammatory genes in the early post-treatment biopsies (2 days after pre-treatment biopsies) and repair and angiogenesis genes in the later (4 to 8 days) biopsies. The fourth and smallest set of genes was down-regulated throughout the study. Early in wound healing the expression of markers of both M1 and M2 macrophages were increased, but later M2 markers predominated.


CONCLUSIONS
The initial response to a cutaneous wound induces powerful transcriptional activation of pro-inflammatory stimuli which may alert the host defense. Subsequently and in the absence of infection, inflammation subsides and it is replaced by angiogenesis and remodeling. Understanding this transition which may be driven by a change from a mixed macrophage population to predominantly M2 macrophages, may help the interpretation of the cellular and molecular events occurring in the microenvironment of serially biopsied tissues.
Deonarine
Kavita
K
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center National Institutes of Health, Bethesda, MD 20892, USA. kavitasoleil@yahoo.com
Panelli
Monica C
MC
Stashower
Mitchell E
ME
Jin
Ping
P
Smith
Kina
K
Slade
Herbert B
HB
Norwood
Christopher
C
Wang
Ena
E
Marincola
Francesco M
FM
Stroncek
David F
DF
D000287:Administration, Topical; D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077271:Imiquimod; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D010919:Placebos; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*
D000634:Aminoquinolines; D015415:Biomarkers; D010919:Placebos; D000077271:Imiquimod