The glycan modulation mechanism of activity vitronectin that induces tissue regeneration and remodeling, or tissue fibrosis

玻连蛋白（VN）是一种多功能糖蛋白，参与组织重塑。之前，我们曾报道VN的糖基化显著改变并增强了胶原结合活性^[1]。本研究以大鼠肝部分切除（PH）、假手术（SH）和非手术（NO）后24 h血浆为材料，采用尿素变性法纯化VN，观察VN对组织溶解系统和细胞铺展活性的影响。PH-或SH-VN与纤溶酶原激活物抑制剂-1（派-1）的结合分别为NO-VN的1/3和2/3。PH-VN和SH-VN的uPA结合率均为No-VN的2倍。结果表明，与NO-VN相比，SH-VN或SH-VN可使uPA活性升高。相反，通过酶处理的VN的去糖基化增强了派-1和uPA结合，因此所得的uPA活性不变，这表明VN的cach配体结合受到内聚糖结构的复杂影响。表明VN的唾液酸化状态显著影响细胞铺展活性。而在肝再生过程中，BHK细胞在VN上的铺展能力稍有下降，但在PH-VN和NO-VN上的铺展能力相似。PH-VN诱导uPA活性增强，从而促进纤溶酶的生成。因此，VN糖基化的变化有助于通过在肝再生的初始阶段增强组织溶解来促进组织重塑。

Vitronectin (VN) is a multifunctional glycoprotein involved in tissue remodeling. Previously, we reported that glycosylation of VN significantly changes and enhances the collagen-binding activity^1). In this study, the effect on tissue lytic system and the cell-spreading activity of VN was focused.Rat VNs were purified after urea-denaturation form plasma 24 hours after partial hepatectomy (PH), sham-operation (SH) and non-operation (NO). The binding of PH-or SH-VN to stabilize plasminogen activator inhibitor-1 (PAI-1) decreased to 1/3 and 2/3, respectively, of that of NO-VN. The uPA-binding of both PH-and SH-VNs increased to 2 times of that of No-VN. Consequently the activites of uPA were increased in the presence of SH-or SH-VN compared with NO-VN. In contrast, deglycosylation of VNs by enzyme treatments enhanced both PAI-1 and uPA binding so that the resultant uPA acitivity was unchanged suggesting that the cach ligand-binding of VN is influenced complexly with the innerglycan structures.The cell spreading activity on VN substrate differed by the kind of cells The spreading of BHK on desialylated VN decreased to 1/2 of that of control VN, indicating that the cell-spreading activity is significantly affected by sialylation state of VN. However, on the VNs during liver regeneration, BHK cells exhibited slightly decreased spreading on SH-VN but similar spreading on PH-VN and NO-VN.PH-VN induced the enhanced uPA activity, which would promote plasmin generation. Therefore, the change in glycosylation of VN contributes to tissue remodeling by enhancing tissue lysis at the initial stage of liver regeneration.