在炎症性肠炎的致病机制中,如何维持肠道内稳态是一个重要的科学问题。巨噬细胞在炎症性肠炎的发病机制中发挥有重要的调控作用，但其具体调节机制仍不清楚。在本项目研究中，我们研究细胞外基质蛋白1（ECM1）分子对炎症性肠炎的保护性机制。我们将重点研究：1)ECM1基因缺失的小鼠与自发性肠炎的关系。2)比较研究ECM1分子的表达水平，在DSS诱导的急性肠炎小鼠模型和溃疡性结肠炎病人中，与疾病表型的对应关系。3)观察ECM1基因缺失的小鼠，对DSS诱导疾病易感性的影响。4) 用ECM1重组蛋白治疗小鼠，观察其对DSS诱导的抑制作用。5) 在机制研究中，重点观察ECM1对巨噬细胞的活化作用和调控致炎因子（IL-6和TNF-a）的释放机制，以及它们影响Treg和Th17细胞的功能。本课题研究ECM1负性调控巨噬细胞的功能和调控炎症肠炎的保护机制，有潜在的生物治疗作用。课题有重要的理论意义和临床应用价值。

In order to keep the homeostasis in bowel system, it is essential to control the inflammation in inflammatory bowel disease (IBD). Macrophage plays an important role in initiating inflammation and controlling the pathogenesis of IBD. However, the mechanism that regulates macrophage function in IBD remains unclear. It is critical issue to find out new endogenous gene/protein which is able to control the function of macrophage. In current study, we will focus on: 1) To observe the occurrence of the spontaneous inflammatory bowel disease (IBD) in extra cellular matrix protein 1(ECM1) gene deletion mice; 2) to measure the expression pattern of ECM1 protein in DSS-induced IBD mice and UC patients; 3) To detect the disease susceptibility to DSS-induced IBD in ECM1-deletion mice. 4) To test whether the treatment of recombinant ECM1 protein is able to protect mice from DSS-induced IBD 5) finally, in mechanism study, we will investigate the negative regulation of ECM1 on inflammatory cytokines (IL-6/TNF-a) production in macrophage and in turn to control the development of T regulatory cell and Th1/Th17 effector cells in DSS-IBD model. To carry on this project will be helpful in understanding new mechanism for IBD induction and designing a new strategy in prevention of IBD disease. Our research will be valuable in theory development and application study in controlling inflammation.