我们前期首次发现外源性给予岩藻糖后上皮细胞岩藻糖基化在维持肠上皮黏膜屏障功能中发挥重要作用，但其对上皮细胞修复的机制不明确。肠上皮修复主要依赖于肠道干细胞（ISC）干性的激活。我们初步发现外源性给予岩藻糖后肠道干细胞岩藻糖基化水平明显增加，而FUT2是调控肠道岩藻糖基化修饰的关键因素，给予岩藻糖后，野生型小鼠肠道干细胞中表达更为丰富的FUT2蛋白，而FUT2-/-小鼠肠道干细胞数量明显减少。因此，FUT2如何参与干细胞干性激活是本课题的研究重点，我们将通过在体和离体干预肠道干细胞FUT2，探讨其可能主要机制在于FUT2介导的岩藻糖基化对干细胞增殖分化的关键信号蛋白Delta/Notch、EphB/EphrinB直接修饰，或通过IL-22介导的间接途径及正反馈效应，促进干细胞干性激活，进而在肠黏膜屏障修复中发挥作用，本项目的实施，将为危重疾病肠道黏膜屏障损伤后修复提供可能的治疗靶点。

We discovered that epithelial cells fucosylation is very important role on maintaining intestinal epithelium mucosa barrier function after giving exogenous fucose, but its mechanism is uncertain. Mucosal barrier disorder recovery relies on intestinal epithelial repair, which mainly depends on the activation of the intestinal stem cells (ISCs). Therefore, how to activate the stemness of ISCs is one of the important targets for epithelial repair. After our preliminary experiment, we find that the level of ISCs fucosylation is increased significantly after giving exogenous fucose and fucosyltransferase2 (FUT2) is the most key factor for regulation of intestinal fucosylation. Furthermore, ISCs express more abundant FUT2 proteins in wild type mice after feeding exogenous fucose. However, the number of ISCs decreased significantly in FUT2-/- mice. So, FUT2 maybe plays an important role in the stemness maintenance of ISCs. FUT2 whether and how to participate in the stemness maintenance of ISCs are the vital items for this research. We will intervene with ISCs of FUT2 in vivo and in vitro respectively in order to find the key molecular mechanism：FUT2 mediated the Delta/Notch or EphB/EphrinB protein fucosylation of ISCs directly, or through the indirect way of IL-22 and positive feedback effect, promoting the stemness maintenance of ISCs and then providing possible target for the critical diseases of intestinal mucosa barrier damage repair.