M. S. Hu1, S. Malhotra1, W. Hong1, M. Januszyk1, G. G. Walmsley1, A. Luan1, D. Duscher1, D. Wan1, G. C. Gurtner1, M. T. Longaker1, P. Lorenz1 1Stanford University,School Of Medicine,Palo Alto, CA, USA
Introduction:
Early fetuses heal without scar formation, yet the biological mechanism behind this process is largely unknown. We aimed to examine fetal fibroblasts, which are intimately involved with the wound healing and scar formation process, in different stages of development to characterize differences that may contribute to the switch from wound regeneration to repair.
Methods:
Fetal fibroblasts were harvested and cultured from the dorsal skin of time-dated BALB/c embryos. Total RNA was isolated and microarray analysis was performed using chips with 42,000 genes. Significance analysis of microarrays (SAM) was utilized to select genes with greater than 2-fold expression differences between the wounds with a false discovery rate (FDR) of less than 2. Enrichment analysis was performed on significant genes to identify differentially expressed pathways.
Results:
Comparison of gene expression profiles revealed 275 genes that were differentially expressed between E14 and E18 fetal fibroblasts, with 30 genes significantly downregulated and 245 genes upregulated at the E18 time point compared to the E14 time point. Ingenuity pathway analysis (IPA) identified the top 20 signaling pathways that were differentially regulated between E14 and E18 fetal fibroblasts.
Conclusion:
This work represents the first instance where differentially expressed genes and signaling pathways between fetal fibroblasts at E14 and E18 have been identified. These genes and pathways drive the mechanism behind the transition from scarless fetal wound regeneration to scarring adult wound repair and may prove to be key targets for future therapeutics aimed to promote regeneration.