BID介导的DNA损伤和天然免疫信号通路是调控上皮细胞恶性转变的重要分子机制，然而肠炎恶变的分子机制和向炎症组织归巢的间充质干细胞(MSCs)在其中的调控作用尚不明确。利用DSS、AOM/DSS诱导肠炎及其相关性肠癌模型和肠上皮、肠癌细胞株为研究对象，采取MSCs尾静脉注射和体外细胞共培养等手段，在干预DNA损伤信号分子ATM、BID和免疫相关分子NOD1/2后，1）分析MSCs在从肠炎到肠癌恶变中所介导的生物学功能，重点研究MSCs的归巢对炎症恶变过程中释放的ROS、RNS致DNA损伤的影响；2）从激活DNA损伤检控点和天然免疫应答的角度，阐明ATM/BID/NOD1/2信号通路是调控肠炎恶性转化的重要分子机制，并进一步明确MSCs对该通路的调节；3）结合正常和炎症性肠病及肠癌病患的临床标本分析，寻找可能的检控蛋白或免疫相关分子作为肠炎恶变的标志分子，为其在临床医学上的应用奠定理论基础。

Mesenchymal stem cells (MSCs) have the ability to home to sites of inflammation and cancer, and BID-mediated DNA damage response and innate immune signaling pathways are the important molecular mechanisms in the progression of malignant transformation of the epithelial cells. However, the malignant transformation mechanisms of colitis and the function roles of MSCs in the colitis-associated cancer are not clear. So this proposal is focused on studying the colitis and colitis-associated cancer models that induced by DSS, AOM/DSS, colon epithelium cells and colon cancer cell lines. In vitro, we use tail vein injection and cell co-cultured, after interference the DNA damage signal moleculars ATM, BID and immune moleculars NOD1, NOD2, confirmed that the biology function of MSCs mediated on chronic enteritis translate to colon cancer. Focus on tumor-homing of MSCs and its effects on the releasing of ROS, RNS during inflammation progression which can cause DNA damage. On the mechanisms, we will clarify that the ATM/BID/NOD1/2 signaling pathways are the major molecular mechanisms to regulate the malignant transformation of colitis by activating DNA damage check-points and natural immune response, furthermore,the function of MSCs in these pathways will be summarized. Simultaneously, we will further analysis some clinical samples of inflammatory bowel disease and colon cancer in order to look for some potential check-point proteins or immune moleculars as a marker of colitis-associated cancer, in order to lay a foundation for the application of clinical medicine.