放射性肠纤维化引起的肠道狭窄、梗阻等症状严重影响腹盆腔放疗病人的生活质量。肠道受到辐射损伤后，首先通过隐窝底部的肠道干细胞再生来修复损伤，但是肠道干细胞再生能力与放射性肠纤维化的关系尚不清楚。我们前期研究发现放射性肠纤维化患者照射野内再生隐窝数量减少，提示肠道干细胞再生能力减弱可能会进展为纤维化，而在小鼠肠道辐射损伤再生过程中Lgr5表达下调，CD44的表达明显上调，提示CD44在肠道损伤再生过程中发挥重要作用。本项目拟利用临床样本、动物模型及肠道类器官培养体系研究肠道干细胞再生与放射性肠纤维化的关系、明确CD44调控肠道干细胞再生进而影响放射性肠纤维化发生的分子机制。本研究将为临床防治放射性肠纤维化的发生提供新思路，有助于研发逆转放射性纤维化的靶向药物。

Radiation induced intestine fibrosis, characterized by stricture or obstruction, significantly affects the life quality of patients who received radiotherapy. Intestinal stem cells located at the bottom of the crypt play important roles during intestine regeneration after irradiation. However, the relationship between the intestinal stem cell regeneration and radiation-induced intestine fibrosis remain unclear. Our previous studies found that the number of regenerated crypts in mucosa involved in the radiation zone was significantly reduced in patients with intestinal fibrosis, indicating that fibrosis might be caused by decreased regeneration ability of intestine stem cells. We also found that in the process of regeneration, the expression of Lgr5 was down-regulated while CD44 was activated, which indicated that CD44 might play a key role during the intestine regeneration. We will utilize clinical samples, animal models and intestinal organoid culture system to investigate the relationship between the intestinal stem cell regeneration and radiation-induced intestine fibrosis and to clarify the molecular mechanisms of how CD44 regulate the intestine stem cell regeneration to reduce intestine fibrosis. Our study will afford a new insight to prevent and contribute to developing target therapy for radiation-induced intestine fibrosis.