Positional differences in the wound transcriptome of skin and oral mucosa.
BACKGROUND
When compared to skin, oral mucosal wounds heal rapidly and with reduced scar formation. Recent studies suggest that intrinsic differences in inflammation, growth factor production, levels of stem cells, and cellular proliferation capacity may underlie the exceptional healing that occurs in oral mucosa. The current study was designed to compare the transcriptomes of oral mucosal and skin wounds in order to identify critical differences in the healing response at these two sites using an unbiased approach.


RESULTS
Using microarray analysis, we explored the differences in gene expression in skin and oral mucosal wound healing in a murine model of paired equivalent sized wounds. Samples were examined from days 0 to 10 and spanned all stages of the wound healing process. Using unwounded matched tissue as a control, filtering identified 1,479 probe sets in skin wounds yet only 502 probe sets in mucosal wounds that were significantly differentially expressed over time. Clusters of genes that showed similar patterns of expression were also identified in each wound type. Analysis of functionally related gene expression demonstrated dramatically different reactions to injury between skin and mucosal wounds. To explore whether site-specific differences might be derived from intrinsic differences in cellular responses at each site, we compared the response of isolated epithelial cells from skin and oral mucosa to a defined in vitro stimulus. When cytokine levels were measured, epithelial cells from skin produced significantly higher amounts of proinflammatory cytokines than cells from oral mucosa.


CONCLUSIONS
The results provide the first detailed molecular profile of the site-specific differences in the genetic response to injury in mucosa and skin, and suggest the divergent reactions to injury may derive from intrinsic differences in the cellular responses at each site.
Chen
Lin
L
Center for Wound Healing & Tissue Regeneration, University of Illinois, Chicago, IL, USA.
Arbieva
Zarema H
ZH
Guo
Shujuan
S
Marucha
Phillip T
PT
Mustoe
Thomas A
TA
DiPietro
Luisa A
LA
D000818:Animals; D015342:DNA Probes / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D025341:Principal Component Analysis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D013997:Time Factors; D014059:Tongue / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*
D015342:DNA Probes; D053583:Interleukin-1beta