Identification of a transcriptional signature for the wound healing continuum.
Bottom Line: Central to these outcomes is the role of the fibroblast.Genes whose expression increases following serum exposure in the order OMF < NF < CWF are candidates for a negative/impaired healing phenotype (the dysfunctional healing group), whereas genes with the converse pattern are potentially associated with a positive/preferential healing phenotype (the enhanced healing group).Sixty-six genes in the enhanced healing group and 38 genes in the dysfunctional healing group were identified.
Affiliation: Wound Biology Group, Cardiff Institute of Tissue Engineering and Repair, Tissue Engineering and Reparative Dentistry, School of Dentistry.Show MeSH
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Mentions: We used a permutation-based test to identify probe sets that were differentially expressed in OMF, NF, and CWF in a pattern consist with a possible role in a wound healing continuum (i.e., those demonstrating an increasing [OMF < NF < CWF] or decreasing [OMF > NF > CWF] expression gradient from one “end” of the continuum to the other). For the differential fibroblast populations, all possible sampling of one OMF sample, one NF sample, and one CWF sample (giving the 112 different samplings of the dataset) were assessed for correlation of this subset to the theoretical profiles of a healing continuum (Supporting Information Figure S2). A total of 112 probe sets displayed patterns of expression consistent with that of an ideal continuum (Supporting Information Figure S3; FDR controlled p < 0.05) and were further subdivided into ascending or descending continuum patterns. The largest group of genes identified by this continuum identification analysis was the enhanced healing group (Figure 4A and Supporting Information Table S2), which showed a descending pattern of expression across the continuum. Sixty-six genes were present within this group, and although they have diverse functions, they do have the common characteristic of having their highest expression in the fetal-like (scarless) oral mucosa and decreasing to their lowest levels in the impaired nonhealing phenotype of the chronic wound (example shown in Figure 5A and C). Thirty-eight genes were present within the dysfunctional healing group (Figure 4B and Supporting Information Table S3) and were at low levels in cells where healing was enhanced and were at increased levels in cells associated with poor wound healing capacities (example shown in Figure 5B and D). One gene (MYLIP) showed a more complex pattern of expression and fell into more than one of the gene expression pattern classifications.
Affiliation: Wound Biology Group, Cardiff Institute of Tissue Engineering and Repair, Tissue Engineering and Reparative Dentistry, School of Dentistry.