USP25调控STAT3依赖性IL-10/IL-22抗炎信号在溃疡性结肠炎中作用及机制研究

Ulcerative colitis (UC) is a kind of elusive, chronic and non-specific inflammatory disease in intestinal tract. Recently, the incidence of UC is gradually increasing without satisfactory clinical treatment. Therefore, it is critical to explore the pathogenesis of UC and find out effective treatment targets. In our previous study, we initiated finding that the knockout of USP25 could up-regulate the expression of IL-10/IL-22 and STAT3, meanwhile, alleviate intestinal inflammation in DSS-induced mice were also detected. Thus, we speculated that USP25 can regulate STAT3-dependent IL-10/IL-22 inflammatory signaling pathway which plays a key role in the development of UC. Based on previous studies, we plan to bred USP25-/-STAT3-/- mice, establish DSS-induced mice models of UC and interfere with the expression of IL-10 / IL-22 in the colon tissues of UC mice. We further detect the expression of STAT3, inflammatory mediators together with intestinal mucosal barrier-related molecule in inflammatory cells and colon tissues from UC mice and patients. The differentially expressed genes and cells were screened and validated at the cellular level. Herein, we aim to clarify the effect and mechanism of USP25 in the occurrence and development of UC in order to offer potential therapeutic methods for UC.

溃疡性结肠炎（ulcerative colitis，UC）是一种病因不明的慢性非特异性肠道炎症性疾病。近年来，UC发病率逐年上升，且临床疗效欠佳，探讨其发病机制并寻找有效治疗靶点意义重大。项目组前期研究首次发现敲除USP25可上调IL-10/IL-22和STAT3表达，减轻DSS诱导小鼠UC模型肠道炎症，推测USP25可能通过调控STAT3依赖性IL-10/IL-22抗炎信号在UC中发挥关键作用。本项目拟培育USP25-/-STAT3-/-小鼠，构建DSS诱导小鼠UC模型并干扰其结肠组织中 IL-10/IL-22的表达，运用生物学技术检测STAT3和IL-10、IL-22等炎症介质及肠黏膜屏障相关分子在UC小鼠和UC患者结肠组织及血清中的表达，筛选差异表达基因和细胞，并在细胞水平进行验证，从而阐明USP25在UC发生发展中的具体作用机制，为UC的临床治疗提供新靶点。

溃疡性结肠炎（ulcerative colitis，UC）是一种病因不明的慢性非特异性肠道炎症性疾病。近年来，UC发病率逐年上升，且临床疗效欠佳，探讨其发病机制并寻找有效治疗靶点意义重大。项目组前期研究首次发现敲除USP25可上调IL-10/IL-22和STAT3表达，减轻DSS诱导小鼠UC模型肠道炎症，推测USP25可能通过调控STAT3依赖性IL-10/IL-22抗炎信号在UC中发挥关键作用。本项目拟培育USP25-/-STAT3-/-小鼠，构建DSS诱导小鼠UC模型并干扰其结肠组织中 IL-10/IL-22的表达，运用生物学技术检测STAT3和IL-10、IL-22等炎症介质及肠黏膜屏障相关分子在UC小鼠和UC患者结肠组织及血清中的表达，筛选差异表达基因和细胞，并在细胞水平进行验证，从而阐明USP25在UC发生发展中的具体作用机制，为UC的临床治疗提供新靶点。