川崎病（Kawasaki disease, KD）为全身免疫性血管炎症，是成年后冠心病的高危因素。我们前期研究发现：KD急性期去线性泛素酶Gumby表达下调；敲减Gumby后，p-STAT3和下游炎症基因表达升高；验证Gumby与STAT3有相互作用，且能去除后者线性泛素。据此推测：KD急性期，Gumby可调控STAT3的去线性泛素化、p-STAT3信号活化及其下游炎性基因表达，从而介导KD炎症。故我们拟研究：①KD病例中Gumby、p-STAT3和炎症因子表达量，及其与冠脉损伤的相关性；②冠脉内皮细胞炎性损伤时，Gumby与STAT3相互作用，过表达/敲除前者后，检测STAT3的线性泛素化和活化情况；③鼠KD模型上，Gumby条件敲除后和对照组比较，其KD血管炎症、冠脉损伤、p-STAT3活化及炎症因子表达改变。旨在阐明Gumby调控KD急性期炎症的分子机制，为其防治提供新理论和新靶点。

Kawasaki disease (KD) is a systemic immune vascular inflammation that is a risk factor for coronary heart disease in adulthood. Our previous study found that the expression level of de-linearized ubiquitinase Gumby was down-regulated during the acute phase of KD; both the expression level of p-STAT3 and its downstream inflammatory genes were increased after knockdown of Gumby; the interaction between Gumby and STAT3 was also verified. Furthermore, the Gumby protein can remove linear ubiquitin from STAT3. Accordingly, we speculated that: during the acute phase of KD, Gumby can regulate the disassembly of linear ubiquitin level of STAT3, the activation of p-STAT3 signaling, the relative expression quantity of its downstream inflammatory genes, and eventually involved in the KD inflammatory responses. Therefore, we plan to conduct the following researches:①analyzing the expression level of Gumby, p-STAT3 and inflammatory genes, examining their correlations with coronary artery injury degree of KD samples;②studying the interactions between Gumby and STAT3, after overexpression or knockout of the Gumby gene, then investigating the linear ubiquitin level of STAT3 and also its signaling activation in the coronary endothelial cells with inflammatory injuries;③in the KD models via using the wide-type or gumby gene conditional knockout mouse, investigating and comparing the symptoms of vascular inflammation, the degree of coronary artery injury, the activation of p-STAT3 signaling and also the expression level of its downstream inflammatory genes. Hence this program aims to elucidate the molecular mechanism of Gumby's regulation in acute inflammatory response of KD, and provide new theories and new targets for the prevention and treatment of KD.