追溯狭窄型疾病行为成为克罗恩病治疗难点的基础医学背景，与之对应的除了疾病进程中慢性炎症因素的反复作用，更重要的是还存在独立于慢性炎症机制以外的肠壁纤维化自我增强体系。本项目基于前期工作中发现的tRNA衍生片段tRF-35-P4R8YP9LON4VN1可能参与克罗恩病肠壁纤维化相关II型上皮-间质转化动态平衡关键环路这一立足点，通过初步分析克罗恩病可能存在的tRNA衍生片段改变→miR-200b-ZEB1/2环路表达或修饰异常→与TGFβ1-SMAD通路交互作用改变→II型上皮-间质转化向间质表型偏移→肠壁纤维化加剧这一作用轴，继而从逆转tRNA衍生片段异常的全新角度，构建维系II型上皮-间质转化平衡、阻断肠壁纤维化进程的基础研究策略，为探究预测克罗恩病肠道纤维性狭窄的潜在生物标志物、获取抑制克罗恩病肠道纤维性梗阻的药物靶点提供新的启迪。

Back to the basic medical background for stenosis disease behavior as therapeutic difficulty in Crohn's disease, in addition to the role of chronic inflammation in the process of the disease, more importantly, there is also a self-reinforcing system of the intestinal wall fibrosis independent of the mechanism of chronic inflammation. This project is based on the critical point of the discovery in the preliminary work that tRNA-derived fragment (tRF-35-P4R8YP9LON4VN1) may be involved in key loop of intestinal fibrosis associated type II epithelial-mesenchymal transition dynamic equilibrium. The axis for change of tRNA-derived fragment→miR-200b-ZEB1/2 loop expression change or modification abnormality→interaction with TGFβ1-SMAD pathway modification→type II epithelial-mesenchymal transition to mesenchymal phenotype shift→intestinal fibrosis exacerbates is analyzed preliminarily. The basic research strategy to maintain the balance of type II epithelial-mesenchymal transition and block the process of intestinal fibrosis are established from the brand new perspective of reversing the abnormality of tRNA-derived fragments. The aim of this project is to provide a new insight into the potential biomarkers for predicting the stricture of Crohn's disease and to obtain the drug targets to inhibit the fibrotic obstruction in the intestine.