Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
Institute of Nephrology, Peking University, Beijing, China.
J Cell Mol Med. 2020 Mar;24(6):3572-3581. doi: 10.1111/jcmm.15046. Epub 2020 Feb 11.
Both Tamm-Horsfall protein (THP) and collectin-11 (CL-11) are important molecules in acute kidney injury (AKI). In this study, we measured the change of glycosylation of THP in patients with AKI after surgery, using MALDI-TOF MS and lectin array analysis. The amount of high-mannose and core fucosylation in patients with AKI were higher than those in healthy controls. In vitro study showed that THP could bind to CL-11 with affinity at 9.41 × 10 mol/L and inhibited activation of complement lectin pathway. The binding affinity decreased after removal of glycans on THP. Removal of fucose completely ablated the binding between the two proteins. While removal of high-mannose or part of the N-glycan decreased the binding ability to 30% or 60%. The results indicated that increase of fucose on THP played an important role via complement lectin pathway in AKI.
Tamm-Horsfall 蛋白（THP）和 collectin-11（CL-11）都是急性肾损伤（AKI）中的重要分子。在这项研究中，我们使用 MALDI-TOF MS 和凝集素阵列分析测量了手术后 AKI 患者 THP 糖基化的变化。AKI 患者的高甘露糖和核心岩藻糖基化含量高于健康对照组。体外研究表明，THP 可以与 CL-11 以 9.41×10 mol/L 的亲和力结合，并抑制补体凝集素途径的激活。THP 上糖基去除后结合亲和力降低。完全去除岩藻糖会完全消除两种蛋白质之间的结合。而去除高甘露糖或部分 N-糖会使结合能力降低至 30%或 60%。结果表明，THP 上岩藻糖的增加通过补体凝集素途径在 AKI 中发挥重要作用。
