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1 Department of Surgery, The Ohio State University Medical Center, Columbus, Ohio, United States
* To whom correspondence should be addressed. E-mail: chandan.sen{at}osumc.edu.
This work represents a maiden effort to systematically screen the transcriptome of the healing wound-edge tissue temporally using high-density GeneChipsTM. Changes during the acute inflammatory phase of murine excisional wounds were characterized histologically. Sets of genes that significantly changed in expression during healing could be segregated into the following five sets: up-early (6-24h; cytokine-cytokine receptor interaction pathway), up-intermediary (12-96h; leukocyte-endothelial interaction pathway), up-late (48-96h; cell-cycle pathway), down-early (6-12h; purine metabolism) and down-intermediary (12-96h; oxidative phosphorylation pathway). Results from microarray and real-time PCR analyses were consistent. Results listing all genes that were significantly changed at any specific time point were further mined for cell-type (neutrophils, macrophages, endothelial, fibroblasts and pluripotent stem cells) specificity. Candidate genes were also clustered on the basis of their functional annotation linking them to inflammation, angiogenesis, reactive oxygen species (ROS) or extracellular matrix (ECM) categories. Rapid induction of genes encoding NADPH oxidase subunits and down-regulation of catalase in response to wounding is consistent with the fact that low levels of endogenous H2O2 is required for wound healing. Angiogenic genes, previously not connected to cutaneous wound healing, that were induced in the healing wound-edge included adiponectin, epiregulin, angiomotin, Nogo and VEGF-B. This study provides a digested database which may serve as a valuable reference tool to develop novel hypotheses aiming to elucidate the biology of cutaneous wound healing comprehensively.
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