炎症性肠病与结直肠癌的发生密切相关，是炎症性肠病相关结直肠癌发生研究领域中的重大科学问题。肠道巨噬细胞活化和炎症因子表达在炎症性肠病炎症-肿瘤恶性转化过程中具有重要作用，其活化的调控机制目前受广泛关注。申请人前期对HNF家族分子HNF4α在结肠癌恶性进展过程中的作用进行了深入研究，结果发表于Mol Carcinogen（IF4.77）。但是，目前仍缺乏HNF家族分子在肠道炎症和肿瘤发生中的系统研究。我们在AOM/DSS小鼠自发结肠癌模型中，系统筛选HNF家族分子在肠道巨噬细胞中的表达，发现HNF 3β表达显著降低。我们因而构建了HNF3β巨噬细胞敲除小鼠，利用AOM/DSS诱导结直肠癌，结果发现巨噬细胞敲除HNF 3β能够显著促进结直肠癌的发生。据此本项目拟研究HNF 3β在肠道巨噬细胞活化及其介导的炎症性肠病相关结直肠癌发生发展中的作用，为寻求新的结肠癌干预靶点提供理论依据和研究基础。

Inflammatory bowel disease was closely associated with colorectal carcinoma and it was the major and cutting-edge scientific problems in the field of inflammatory bowel disease (IBD)-associated colorectal cancer. Bowel macrophages activation and inflammatory cytokine production played important roles in IBD-related colorectal carcinoma carcinogenesis and the molecular mechanisms have attracted much attention . We previously reported the roles of HNF family member HNF4α in intentinal cancer aggravation (Mol Carcinogen). However, the roles of HNF family members in IBD- associated colorectal cancer have not been well characterized..Here we systematically examined the expression of HNF family members in bowel macrophages of AOM/DSS-induced colorectal cancer, and found that HNF 3β expression was significantly decreased. We therefore constructed the conditional macrophage-specific HNF3βknockout mouse and found that the deficiency of HNF3β significantly promoted the development of the colorectal cancer in the AOM/DSS-induced colorectal cancer mouse model. Hence, this project intends to study the roles of HNF 3β in the regulation of intestinal macrophage activationand IBD-associated colorectal cancer carcinogenesis . These results might provide theoretical basis and research foundation for HNF3β becoming a new intervention therapeutic targets for colorectal carcinoma.