UC的发病率逐年升高，治疗效果仍不理想，主要因其发病机制尚不清楚。在前期工作中，我们已经证实ER stress/Puma信号通路在结肠炎中发挥着重要作用（J Clin Invest），我们进一步研究显示β-arrestin-2对结肠炎有重要的调控作用（Mucosal Immunol; Am J Pathol）。最近，我们的研究又发现在结肠炎小鼠模型中，β-arrestin-2对结肠炎黏膜上皮的Beclin1等自噬蛋白可能存在着调控作用，并且这种调控可能通过ER-stress/PUMA通路发挥作用，但具体调控机制尚不清楚。本项目拟在上述研究基础上，利用β-arrestin-2基因缺陷小鼠结肠炎模型、肠上皮细胞系及结肠炎患者肠黏膜样本，探讨β-arrestin-2是否通过ER-stress/PUMA调控结肠黏膜的自噬，并阐明其在结肠炎发生发展中的作用和机制，为结肠炎的新药开发提供科学依据。

The incidence of ulcerative colitis is increasing year by year, the treatment of which is still not satisfactory, mainly due to the unknown of its pathogenesis. In previous work, we have demonstrated that ER stress / PUMA signaling pathway plays an important role in colitis (J Clin Invest). Our further study show that β-arrestin-2 has an important regulatory effect on colitis (Mucosal Immunol; Am J Pathol). Recently, we have also found that β-arrestin-2 may regulate Beclin1 signal of colitis in colitis mouse mode, and this regulation may be achieved.through the ER stress / PUMA, but the specific mechanism is not well known. Therefore, based on the above study, we will be aiming to investigate whether β-arrestin-2 regulates the autophagy of colonic mucosa through ER stress / PUMA utilizing β-arrestin-2 gene-deficient murine colitis model, intestinal epithelial cell line and colonic mucosa in colitis patients, to clarify its role in the occurrence and development of colitis and to provide a scientific basis for new drugs.