Methods: Oral mucosal or chronic wound fibroblasts were isolated from n=4 patients and compared to patient matched ‘normal' dermal skin fibroblasts. Cells were serum starved for 48 hours followed by re-stimulation with serum. RNA was isolated 0 and 6 hours after serum stimulation and gene expression analysed by Affymetrix™ cDNA Microarray. Meta-analysis of this experimental data was undertaken to characterize the expression patterns of serum responsive genes.
Results: Following identification of genes differentially regulated by serum exposure, meta-analysis identified multiple patterns of expression with continuum-like characteristics. These include genes which were serum induced to descending or ascending levels across the sampled continuum. The former included BMP2, whose expression displayed high levels of serum induction in OMFs (684), which was reduced in NDFs (350/197) and further reduced in CWFs (71). An alternative pattern of increasing induction was observed in the expression of, for example, epiregulin, with low induction in OMFs (42), increased in NDFs (48/55) and highest in CWFs (138). Similar ascending and descending patterns were also observed in serum repressed genes.
Conclusions: 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.
Acknowledgements: We would like to thank the NC3Rs for funding this research.