The α1,3-fucosyltransferase FUT7 regulates IL-1β-induced monocyte-endothelial adhesion via fucosylation of endomucin
The α1,3-fucosyltransferase FUT7 regulates IL-1β-induced monocyte-endothelial adhesion via fucosylation of endomucin
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α1,3-岩藻糖基转移酶 FUT7 通过内粘蛋白岩藻糖基化调节 IL-1β 诱导的单核细胞内皮粘附
DOI：
10.1016/j.lfs.2017.11.017
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发表时间：
2018-01-01
期刊：
影响因子：
6.1
通讯作者：
Yu, Chao
中科院分区：
文献类型：
--
作者：
Zhang, Jun;Ju, Nana;Yu, Chao
单核细胞-内皮细胞粘附是动脉粥样硬化早期的标志性特征，新的证据表明血管粘附分子及其配体的糖基化参与了这一过程。然而，这一过程的机制仍然没有完全阐明。在这项研究中，我们报道了用炎症因子白细胞介素-1 β（IL-1 β）治疗显著上调EA中α 1，3-岩藻糖基转移酶VII基因（FUT 7）mRNA和蛋白表达水平。hy 926内皮细胞。此外，FUT 7过表达显著促进单核细胞-内皮细胞粘附，而FUT 7敲低明显抑制IL-1 β诱导的单核细胞-内皮细胞粘附。进一步的分析表明，选择素配体内粘蛋白的岩藻糖基化直接参与IL-1 β诱导的单核细胞-内皮细胞粘附。最后，我们证明p38和细胞外信号调节激酶（ERK）MAPK信号通路被IL-1 β激活，而抑制p38/ERK信号通路降低FUT 7表达水平和IL-1 β诱导的单核细胞-内皮细胞粘附。总之，这些结果提供了一个新的见解，FUT 7介导的岩藻糖基化有助于动脉粥样硬化的起始和进展。
Monocyte-endothelial adhesion is a hallmark feature of atherosclerosis at early stage and emerging evidence suggests that the glycosylation of vascular adhesive molecules and its ligands is involved in this process. Nevertheless, the mechanism underlying this process remains incompletely elucidated. In this study, we reported that treatment with inflammatory factors interleukin-1 beta (IL-1 beta) pronouncedly upregulated alpha 1,3-fucosyltransferase VII gene (FUT7) mRNA and protein expression level in EA. hy926 endothelial cells. Moreover, FUT7 overexpression significantly promoted monocyte-endothelial adhesion, while FUT7 knockdown obviously inhibited IL-1 beta-induced monocyte-endothelial adhesion. Further analysis demonstrated that fucosylation of selectin ligand endomucin was directly involved in IL-1 beta-induced monocyte-endothelial adhesion. Finally, we demonstrated that p38 and extracellular signal-regulated kinase (ERK) MAPK signaling pathway was activated by IL-1 beta, while inhibition of p38/ERK signaling pathway decreased FUT7 expression level and IL-1 beta-induced monocyte-endothelial adhesion. In summary, these results provide a novel insight that FUT7-mediated fucosylation contribute to the initiation and progression of atherosclerosis.