Vitronectins produced by human cirrhotic liver and CCl4-treated rats differ in their glycosylation pattern and tissue remodeling activity
Vitronectins produced by human cirrhotic liver and CCl4-treated rats differ in their glycosylation pattern and tissue remodeling activity
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DOI：
10.1002/2211-5463.12616
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发表时间：
2019-04-01
期刊：
影响因子：
2.6
通讯作者：
Ogawa, Haruko
中科院分区：
文献类型：
--
作者：
Date, Kimie;Suzuki, Risa;Ogawa, Haruko
肝硬化（Liver Cirrhosis，LC）是一种以细胞外基质（extracellular matrix，ECM）蛋白的病理性积聚和改变为特征的疾病，胶原和玻连蛋白（vitronectin，VN）之间的相互作用被认为是控制肝硬化ECM重塑的关键。如果能够控制VN上寡糖的修饰，就有可能延缓肝硬化的进展。在这项研究中，我们研究了VN糖基化的变化和活动有关的肝组织在人类LC和大鼠模型的LC使用四氯化碳（CCl 4）的重塑之间的关系。人LC中VN的血浆浓度下降到正常血浆中的约三分之二，但具有胶原结合活性的活性VN的比率在LC血浆中增加2.8倍。与此相反，纯化的LC-VN表现出类似的结合活性对I型，IV型和V型胶原的正常VN。LC-VN的凝集素反应性和碳水化合物分析表明，分支，岩藻糖基化和唾液酸化的N-聚糖高于正常VN。另一方面，大鼠血浆中CCl_4-VN水平升高，血浆中活性分子与胶原的比例降低。在CCl 4-VN的碳水化合物中未检测到LC-VN的岩藻糖基化增加。大鼠VN的变化，由于CCl 4治疗不对应于LC引起的人VN的血浆水平的变化，活性分子的比例，或碳水化合物的组成，从而表明，CCl 4处理的大鼠是不是一个合适的模型，研究人类LC中的VN。葡萄糖苷酶处理VN支持这样的假设，即VN的胶原结合活性通过LC期间糖基化的改变来调节，这可能有助于（a）VN的基质掺入和（B）组织纤维化。
Liver cirrhosis (LC) is a disease characterized by pathological accumulation and alteration of extracellular matrix (ECM) proteins; the interaction between two such proteins, collagen and vitronectin (VN), is considered to be the key to controlling ECM remodeling in liver cirrhosis. If it is possible to control the modification of oligosaccharides on VN, it may be possible to retard progression of liver cirrhosis. In this study, we examined the relationship between changes in VN glycosylation and activity related to the remodeling of hepatic tissue in human LC and a rat model of LC generated using carbon tetrachloride (CCl4). Plasma concentrations of VN in human LC declined to approximately two-thirds that in normal plasma, but the ratio of active VN, which has collagen-binding activities, increased 2.8 times in LC plasma. In contrast, purified LC-VN exhibited similar binding activities toward type I, IV, and V collagens to those of normal VN. Lectin reactivities and carbohydrate analyses of LC-VN revealed that branching, fucosylation, and sialylation of N-glycans were higher than those of normal VN. On the other hand, the plasma level of rat CCl4-VN increased and the ratio of active molecules to collagen in plasma decreased. Increased fucosylation of LC-VN was not detected in carbohydrates of CCl4-VN. The changes in rat VN due to CCl4 treatment did not correspond to the changes in plasma levels of human VN caused by LC, the ratio of active molecules, or carbohydrate composition, thereby indicating that CCl4-treated rats are not an appropriate model for studying VNs in human LC. Glycosidase treatment of VNs supported the hypothesis that the collagen-binding activity of VN is modulated by alterations of glycosylation during LC, which may contribute to (a) the matrix incorporation of VN and (b) tissue fibrosis.