Identifying a Gene signature for the wound healing continuum [Abstract]

Introduction: There is a deleterious effect upon wound healing functionality associated with increasing age with a continuum between old and young. Oral mucosal fibroblasts (OMFs) display rapid, scarless, wound healing and represent a young ‘enhanced’ wound healing phenotype. At the other extreme, ‘aged’ chronic wound fibroblasts (CWFs) display an impaired wound healing phenotype. Between these extremes lie normal dermal fibroblasts (NDFs) which have an intermediate healing phenotype. Aim: To identify a signature group of genes whose pattern of expression correlates to the wound healing continuum. Methods/Results: Primary OMFs and CWFs were compared to patient matched NDFs (n=3 and n=4 respectively). Early passage cultures were ‘serum starved’ for 48 hours and re-stimulated with serum, modelling an in vivo wound response. RNA isolated 0 and 6 hours after serum stimulation was analysed by AffymetrixTM cDNA Microarray. Comparison of serum modulated genes in OMFs, NDFs and CWFs to ascending/ descending continuum patterns identified 221 genes with continuum-like expression characteristics including genes which were serum induced or repressed to descending or ascending levels across the sampled continuum. For example, BMP2 expression displayed high levels of serum induction in OMFs (684), which was reduced in NDFs (350/197) and further reduced in CWFs (71). Conclusion: This analysis demonstrated that there are a number of genes displaying a continuum-like pattern of expression and may help in the identification of gene expression signatures for wound healing