Positional differences in the wound transcriptome of skin and oral mucosa

Abstract

BackgroundWhen 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.ResultsUsing 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.ConclusionsThe 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.

Delayed skin wound repair in proline-rich protein tyrosine kinase 2 knockout mice

“…Furthermore, gene expression analyses reveal that MMP-1, MMP-9, and MMP-10 are transcriptionally induced in Pyk2-overexpressing keratinocytes and, therefore, may function as candidate effectors of Pyk2 to promote wound healing. Consistent with this assumption, wound transcriptome profiling revealed that the MMP group of genes that included MMP-1, MMP-9, and MMP-10 genes was a significantly enriched category among early upregulated genes in murine skin wounds, along with two additional MMPs, MMP-8t and MMP-13 (4). MMP gene expression is primarily regulated at the transcriptional level (reviewed in Ref.…”

Differential Apoptosis in Mucosal and Dermal Wound Healing

“…In a recent study, the overall gene expression of mucosal and skin wounds was compared via microarray analysis. 5 Among the multiple differences that were noted, the data suggested that wound healing in these two tissues might exhibit differential signatures of apoptosis related genes, such as tumor necrosis factor alpha (TNF-a) and several downstream signaling factors. 5 Apoptosis can be induced via two main pathways, termed intrinsic and extrinsic.…”

“…4 Altogether, the phases of wound healing after mucosal injury are shortened in duration and generally have reduced gene and protein expression changes in comparison to skin wound healing. 5 Apoptosis is an important mechanism for cellular elimination during wound healing and maintains tissue homeostasis in normal, uninjured tissue. In a recent study, the overall gene expression of mucosal and skin wounds was compared via microarray analysis.…”

Human Wound-Healing Research: Issues and Perspectives for Studies Using Wide-Scale Analytic Platforms

“…Furthermore, several categories of genes were overexpressed in cultured skin substitutes compared with native skin, including genes associated with hyperproliferative skin or activated keratinocytes. 18 In another study, Chen et al 19 investigated why oral mucosal wounds heal more rapidly and with reduced scar formation than cutaneous wounds. They obtained biopsies of both oral mucosal and skin wounds and used microarrays to compare transcriptomes to determine the critical differences in the healing response at these two sites.…”

“…Their results demonstrated dramatically different reactions to injury between skin and mucosal wounds. 19 In a study by Greco et al, 20 the gene expression profiles of thermally injured human skin were observed with microarrays. For the analysis, skin samples were…”