Exogenous l-fucose protects the intestinal mucosal barrier depending on upregulation of FUT2-mediated fucosylation of intestinal epithelial cells
Exogenous l-fucose protects the intestinal mucosal barrier depending on upregulation of FUT2-mediated fucosylation of intestinal epithelial cells
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DOI：
10.1096/fj.202002446rrrr
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发表时间：
2021-07-01
期刊：
影响因子：
4.8
通讯作者：
Lin, Rong
中科院分区：
文献类型：
--
作者：
Li, Ying;Jiang, Yudong;Lin, Rong
FUT 2是一种使用l-岩藻糖介导肠上皮细胞岩藻糖基化的蛋白质，是IBD患者中检测到的基因变体之一。我们的目的是研究外源性l-岩藻糖是否可以作为肠内营养补充剂来保护肠屏障功能。研究了l-岩藻糖对DSS诱导的结肠炎小鼠模型和LPS刺激的Caco-2细胞中上皮屏障功能恢复的影响，并检查了对上皮细胞岩藻糖基化的影响。DSS诱导的结肠炎的严重程度被l-岩藻糖显著降低。检测到l-岩藻糖对上皮屏障功能的恢复。在Caco-2细胞中观察到直接l-岩藻糖介导的紧密连接保护。此外，外源性l-岩藻糖促进了l-岩藻糖的外源性代谢途径，促进了上皮细胞在体内和体外的岩藻糖基化。此外，FUT 2基因的敲除抑制岩藻糖基化和l-岩藻糖对屏障功能的保护作用。在Fut 2基因敲除小鼠中，l-岩藻糖没有改善结肠炎的严重程度。因此，我们得出结论，外源性L-岩藻糖通过上调FUT 2介导的肠上皮细胞岩藻糖基化来保护肠屏障功能并减轻肠道炎症。
FUT2, a protein that uses l-fucose to mediate fucosylation of intestinal epithelial cells, is one of the detected gene variants in IBD patients. We aimed to investigate whether exogenous l-fucose could be an enteral nutritional supplement to protect intestinal barrier function. The effect of l-fucose on the restoration of epithelial barrier function in both the DSS-induced colitis mouse model and LPS-stimulated Caco-2 cells was investigated, and the impact on fucosylation of epithelial cells was examined. The severity of DSS-induced colitis was significantly reduced by l-fucose. Restoration of epithelial barrier function by l-fucose was detected. Direct l-fucose-mediated protection of tight junctions was observed in Caco-2 cells. Moreover, exogenous l-fucose promoted the exogenous metabolic pathway of l-fucose, and fucosylation of epithelial cells both in vivo and in vitro. Moreover, knockout of the FUT2 gene restrained fucosylation and the protective effect of l-fucose on barrier function. The severity of colitis was not improved by l-fucose in Fut2 knockout mice. Therefore we conclude that exogenous l-fucose protects intestinal barrier function and relieves intestinal inflammation via upregulation of FUT2-mediated fucosylation of intestinal epithelial cells.