Molecular mechanism of scarless wound healing its application for therapy of epidermolysis bullosa

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In order to investigate the molecular mechanism of scarless wound healing and identify its specific gene/protein, that is, master gene/protein, we analyzed gene expression in the fetal mouse skin, which scarless wound healing is observed, by differential display and serial analysis gene expression techniques. Differential display analyses revealed that over ten kinds of scarless wound healing-related genes including genes previously reported such as fibromodulin, glycophorin, HOX and PRX families, TGF-beta, PDGH and EGF genes were detected. Furthermore several unknown genes were also detected. Serial analysis gene expression analyses detected over twenty kinds of genes including unknown genes However, introductions the expression vector of each gene or its recombinant protein into the wounds of adult mice skin did not disappear scar formation. Therefore, each gene identified in this study was not master gene of scarless wound healing. Hyaluronic acid is specifically accumulated in the dermis where scarless wound healing is observed, suggesting hyaluronic acid is one of crucial modulator of mechanism of scarless wound healing. Therefore, we next investigated hyaluronic acid rich environment specific genes. Serial analysis gene expression analyses of cultured human dermal fibroblasts containing high amounts of hyaluronic acid revealed similar results to these detected in scarless wound healing. Thirty five hyaluronic acid rich environment specific genes were detected. Seven of them were unknown. Howerver, introduction of these genes into wounded skin also did not disappear scar formation. These results suggest that all genes identified in this study are not master gene but specific gene of scarless wound healing. Therefore, further novel analysis methods and strategies are necessary to find unknown master gene.