衰老机体中成纤维细胞缺失从而抑制小鼠肠炎损伤修复及肠炎相关肠癌发生的作用和机制研究

癌症是一种衰老相关疾病，除随年龄增长细胞积累更多突变而增加患癌风险外，近年来研究发现组织微环境对癌症进展也有重要作用。因此，研究衰老机体中组织微环境如何调控癌症进展有重要意义。我们长期从事肠“炎-癌”相关研究，在年轻和衰老的小鼠体内建立AMO+DSS诱发的肠“炎-癌”模型，发现与年轻机体相比衰老机体的肠炎损伤修复过程变慢，并抑制肠癌发生和发展。初步研究发现损伤修复过程中衰老机体的肠组织中成纤维细胞数量明显减少，进一步研究发现参与损伤修复的成纤维细胞可能是肠道平滑肌细胞转变而来，但调控机制不清楚，也未见文献报道。因此，本课题将利用多种条件敲除小鼠以及小动物肠镜、体内细胞谱系示踪、肠原代细胞分离培养、肠类器官培养、基因表达谱分析、多色免疫荧光等技术，对衰老机体中成纤维细胞如何调控肠炎损伤修复和肠炎相关肠癌进展的机制进行深入研究，将为组织微环境调控肠癌发生和发展提供新的认识，为癌症防控奠定基础。

Abstract: Ageing is the biggest risk factor for cancer. The factors that contribute to age-related increases in cancer are thought to include accumulation of mutations within incipient tumor cells. However, the influence of age-related microenvironment on cancer initiation remains poorly understood. Here We used acute colitis model and colitis-associated-caner model in mice to explore the association between age-associated microenvironment and caner initiation. we find that aged mice significantly delay colitis-associated wound healing and inhibit colitis-associated-cancer initiation. Further，we find localized decreased fibroblast in aged mice may contribute to this difference .However, the mechanism in aged mice that leads to decrease in fibroblast is still unclear. Next, we will use in vivo chromoendoscopy system、Lineage-tracing system、Conditional knockout mice、Gene expression profile analysis、Intestinal organ culture、Multiplex immunohistochemistry technology to continuely uncover the mechanism ,which will help us to understand the relationship between ageing and cancer .