Research on biological function of ryudocan by knockout mice analysis.

纤维粘连蛋白的两个结构域提供了两种不同但相互协作的信号，这是形成局部粘连所必需的。来自细胞结合域的信号是由整合素介导的，而来自肝素结合域的信号是由硫酸乙酰肝素蛋白多糖识别的，其中syndecan-4(Ryudocan)被认为参与了局灶性粘连的形成。我们产生了Syndecan-4基因缺陷的小鼠，以直接研究它的作用。即使在svndecan-4基因缺陷小鼠的成纤维细胞中，也会形成局灶性粘连，当它们被培养在涂有纤维连接蛋白或其细胞结合片段和肝素结合片段的盖片上时，肌动蛋白纤维通常在局灶性粘连处终止。然而，当细胞培养在细胞结合片段上并在培养液中加入肝素结合片段时，与野生型细胞相比，syndecan-4缺失的成纤维细胞的局部黏附形成受到损害。因此，Syndecan-4对于促进…是必不可少的只有当纤维连接蛋白的肝素结合区的信号以可溶形式传递时，才会形成更多的局灶性粘连，最有可能的是从根尖表面传递。当信号以底物结合的形式传递时，其他分子(S)也参与了信号的接收(S)。Syndecan-4在11.5天后肾间充质的输尿管芽中可检测到表达，并在集合管、远端肾小管、肾小球和肾小管间的部分毛细血管中持续表达，直至成熟肾期。然而，在Syndecan-4缺陷[Synd4(-/-)]小鼠中，肾脏的器官发生是正常的。虽然Synd4(-/-)小鼠的大部分肾功能没有受损，但对k-角叉菜胶引起的肾损伤的易感性显著增加。K-卡拉胶严重沉积在Synd4(-/-)小鼠的集合管中，引起梗阻性肾病。导致24只Synd4(-/-)小鼠中有7只在给药后7天内死亡，而24只Synd4(+/+)小鼠无一死亡。给予K-卡拉胶后，叙利亚4(-/-)小鼠的血尿素氮显著高于Synd4(+/+)小鼠，K-卡拉胶与肾髓质膜组分有亲和力，其结合被肝素抑制。因此，Syndecan-4可能通过其肝素硫酸盐起到防止k-卡拉胶在收集管道中沉积的作用。较少

Two domains of fibronectin deliver two different but cooperative signals required for focal adhesion formation. The signal from the cell-binding domain is mediated by integrins, whereas the signal from the heparin binding domain is recognized by heparan sulfate proteoglycans, of which syndecan-4 (ryudocan) has been hypothesized to be involved in focal adhesion formation. We generated mice deficient in syndecan-4 to study its role directly. Even in fibroblasts from svndecan-4-deficient mice, focal adhesions were formed, and actin fibers terminated normally at focal adhesions when they were cultured on coverslips coated with fibronectin or with a mixture of its cell-binding and heparin binding fragments. However, when the cells were cultured on the cell-binding fragment and the heparin-binding fragment was added to the medium, focal adhesion formation was impaired in the syndecan-4 null fibroblasts as compared with that in wild-type cells. Therefore, syndecan-4 is essential for promoting … More focal adhesion formation only when the signal of the heparin-binding domain of fibronectin is delivered as a soluble form, most probably from the apical surface. When the signal is delivered as a substratum-bound form, other molecule(s) also participate(s) in the signal reception.The expression and roles of syndecan-4 in the kidney were investigated. Syndecan-4 expression was detected in the ureteric bud invaginating into the metanephric mesenchyme at 11.5 gestational days, and remained in the collecting ducts, distal renal tubules, glomeruli and some capillaries between renal tubules until the mature kidney stage. However, organogenesis of the kidney was normal in syndecan-4-deficient [Synd4(-/-)] mice. Although most of renal functions of Synd4(-/-) mice were not impaired,significant increase of susceptibility to the k-carrageenan-induced renal damage was observed in Synd4(-/-) mice. K-Carrageenan was deposited severely in the collecting ducts of Synd4(-/-) mice and caused obstructive nephropathy. Leading to death of 7 of 24 Synd4(-/-) mice within 7 days after administration, whereas none of 24 Synd4(+/+) mice died. After the administration ofk carrageenan, blood urea nitrogen of Syrid4(-/-) mice was significantly higher than that of Synd4(+/+) mice, k-Carrageenan had affinity to the membrane fraction derived from the medulla of the kidney, and its binding was inhibited by heparin. Thus, syndecan-4 may function to prevent k-carrageenan deposition in the collecting ducts via its heparan sulfates. Less