Liver fibrosis is a continuous wound healing response caused by chronic liver injury, and the activation of hepatic stellate cells (HSCs) is considered as the main event for it. Core fucosylation catalyzed by FUT8 refers to adding the fucosyl moiety to the innermost GlcNAc residue of N-linked oligosaccharides and is involved in many biological processes such as cell differentiation, migration, and signaling transduction. Aberrant core fucosylation is associated with a variety of diseases including cardiovascular disease, tumors and neuroinflammation, but much less is understood in liver fibrosis. Herein, we reported FUT8 mRNA level was increased in patients with liver fibrosis from GEO database and positively correlated with fibrosis progression. FUT8 expression and the core fucosylation were also elevated in TAA-induced mouse liver fibrosis model, and were mainly distributed in the fibrous septum of mouse liver. TGF-β1, as the most pro-fibrogenic cytokine, could promote the expression of FUT8 and total core fucosylation levels in HSCs in vitro. However, up-regulation of FUT8 in turn inhibited TGF-β1-induced trans-differentiation, migration and pro-fibrogenic signaling pathways in HSCs. In conclusion, our results suggest that the up-regulation of FUT8 inhibits TGF-β1-induced HSC activation in a negative feedback loop, and provide potential new therapeutic strategy for liver fibrosis by targeting FUT8.

肝纤维化是慢性肝损伤引起的持续性伤口愈合反应，肝星状细胞（HSC）的激活被认为是其主要事件。 FUT8催化的核心岩藻糖基化是指将岩藻糖基部分添加到N-连接寡糖最里面的GlcNAc残基上，参与细胞分化、迁移和信号转导等许多生物过程。异常的核心岩藻糖基化与多种疾病有关，包括心血管疾病、肿瘤和神经炎症，但对肝纤维化的了解却少之又少。在此，我们从 GEO 数据库中报道肝纤维化患者中FUT8 mRNA 水平升高，并且与纤维化进展呈正相关。 FUT8表达和核心岩藻糖基化在TAA诱导的小鼠肝纤维化模型中也升高，并且主要分布在小鼠肝脏的纤维间隔中。 TGF-β1作为最促纤维化的细胞因子，在体外可以促进HSC中FUT8的表达和总核心岩藻糖基化水平。然而，FUT8 的上调反过来又抑制了 TGF-β1 诱导的 HSC 转分化、迁移和促纤维化信号通路。总之，我们的结果表明，FUT8 的上调在负反馈环路中抑制 TGF-β1 诱导的 HSC 激活，并通过靶向 FUT8 为肝纤维化提供潜在的新治疗策略。