Institute of Life Sciences, College of Pharmacy, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China.
Institute of Life Sciences, College of Pharmacy, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China.
Biochem Biophys Res Commun. 2018 Jun 2;500(2):249-255. doi: 10.1016/j.bbrc.2018.04.053. Epub 2018 Apr 16.
Monocyte transendothelial migration is a critical step in the initial stage of atherosclerosis, in which the involvement of α-2,6 sialyltransferase 1 (ST6GAL1) has been confirmed by increasing evidence. But the direct relationship between ST6GAL1 and atherosclerosis remains incompletely uncertain. In this study, we demonstrated that the expression level of ST6GAL1 in vascular endothelium was significantly decreased in atherosclerosis development process, while obviously recovered after atherosclerosis regression. Further analysis showed that knockdown of ST6GAL1 by RNA interference in vascular endothelial cells EA. hy926 obviously promoted TNFα-triggered monocyte-transendothelial migration, whereas overexpression of ST6GAL1 strongly inhibited monocyte-transendothelial migration. Moreover, we firstly found β-catenin is a sialylated protein and its sialylation level is decreased in TNFα-treated EA. hy926 cells, suggesting that the function of ST6GAL1 in preventing both atherosclerosis development and monocyte transendothelial migration might result from the sialylation of β-catenin of endothelium. Our results suggested ST6GAL1 might be a potential target for atherosclerosis prevention and treatment.
单核细胞跨内皮迁移是动脉粥样硬化初始阶段的一个关键步骤，越来越多的证据证实了 α-2,6 唾液酸转移酶 1（ST6GAL1）的参与。但 ST6GAL1 与动脉粥样硬化之间的确切关系仍不完全确定。在这项研究中，我们证明了 ST6GAL1 在血管内皮中的表达水平在动脉粥样硬化发展过程中显著降低，而在动脉粥样硬化消退后明显恢复。进一步的分析表明，血管内皮细胞 EA.hy926 中 ST6GAL1 的 RNA 干扰敲低明显促进了 TNFα 触发的单核细胞跨内皮迁移，而 ST6GAL1 的过表达则强烈抑制了单核细胞跨内皮迁移。此外，我们首次发现β-连环蛋白是一种唾液酸化蛋白，其唾液酸化水平在 TNFα 处理的 EA.hy926 细胞中降低，表明 ST6GAL1 在预防动脉粥样硬化发展和单核细胞跨内皮迁移中的作用可能源于内皮细胞中β-连环蛋白的唾液酸化。我们的结果表明，ST6GAL1 可能是预防和治疗动脉粥样硬化的一个潜在靶点。
