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

表皮角质形成细胞的凋亡和分化在皮肤创面愈合中起重要作用。由于ASK1调节角质形成细胞的凋亡和分化，因此ASK1可能调节皮肤创伤愈合。除ASK1外，同样调节细胞凋亡的PI3激酶也可能有助于皮肤伤口的愈合。培养的人角质细胞损伤后，检测JNK和p38MAPK活性。损伤激活了JNK和p38 MAP激酶，提示ASK1-JNK和-p38 MAP激酶的激活是级联反应。细菌感染会阻碍皮肤伤口的愈合。分析细菌感染对角质形成细胞的影响。细菌与培养的角质形成细胞接触诱导产生抗菌肽。接下来，我们分析了PI3激酶是否调节角质肌细胞的分化。分化诱导K1、K10mRNA表达。这种诱导作用被活性PI3激酶的表达减弱，表明PI3激酶通过细胞凋亡和分化来调节皮肤伤口的愈合。小鼠背部创面形成后，组织学观察创面愈合过程，TUNEL法检测周围皮肤角质形成细胞凋亡情况。免疫组织化学染色显示表皮角质形成细胞表达ASK1。综上所述，ASK1通过调节表皮角质形成细胞的凋亡和分化，在皮肤创面愈合中发挥重要作用。

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.