Role of keratinocyte apoptosis and differentiation regulated by ASK1 in wound healing

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Apoptosis and differentiation of epidermal keratinocyte play an important role in skin wound healing. Since, ASK1 regulates apoptosis and differentiation of keratinocyte, ASK1 may regulate skin wound healing. In addition to ASK1, PI3 kinase, which also regulates apoptosis, may contributes skin wound healing. After damage of the cultured human keratinoycte, JNK and p38 MAP kinase activity was analyzed. The damage activated the JNK and p38 MAP kinase, suggesting the activation of ASK1-JNK, and -p38 MAP kinase cascades. Bacterial infection retards skin wound healing. The effect of bacterial infection on keratinocyte was analyzed. Contact of bacteria to cultured keratinocyte induced the production of anti-microbacterial peptides. Next we analyzed whether PI3 kinase regulate keratinoycte differentiation. Differentiation induced the expression of K1 and K10 mRNA. This induction was reduced by expression of active PI3 kinase, indicating that PI3 kinase regulates skin wound healing by apoptosis and differentiation. After formation of wound on the back of mouse, the process of wound healing was histological observed.Keratinocyte apoptosis was detected with TUNEL method on the surrounding skin. Immunohistochemical staining showed that the expression of ASK1 on the epidermal keratinocytes. In conclusion, ASK1 plays an important role in skin wound healing by regulating apoptosis and differentiation of epidermal keratinoycte.