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

玻璃体连接蛋白（VN）是一种参与组织重塑的多功能糖蛋白。先前，我们报道了VN的糖基化显著改变并增强胶原结合活性^1)。本研究主要探讨了VN对组织分解系统和细胞扩散活性的影响。大鼠肝部分切除（PH）、假手术（SH）和非手术（NO）后24小时经血浆尿素变性纯化VNs。ph -或SH-VN结合稳定纤溶酶原激活物抑制剂-1 （PAI-1）的能力分别下降到NO-VN的1/3和2/3。ph - vns和SH-VNs的upa结合均增加到No-VN的2倍。因此，与NO-VN相比，sh -或SH-VN存在时uPA的活性增加。相比之下，通过酶处理的VN去糖基化增强了PAI-1和uPA的结合，从而使最终的uPA活性保持不变，这表明VN的每一个配体结合都受到内聚糖结构的复杂影响。细胞在VN底物上的扩散活性因细胞种类不同而不同，BHK在去盐化VN上的扩散下降到对照VN的1/2，说明细胞的扩散活性受到VN唾液化状态的显著影响。然而，在肝再生过程中，BHK细胞在SH-VN上的扩散略有减少，但在PH-VN和NO-VN上的扩散相似。PH-VN诱导uPA活性增强，促进纤溶酶生成。因此，VN糖基化的改变通过促进肝脏再生初期的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.