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Vitronectins produced by human cirrhotic liver and CCl(4)‐treated rats differ in their glycosylation pattern and tissue remodeling activity

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 possibl...

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Detalles Bibliográficos
Autores principales: Date, Kimie, Suzuki, Risa, Oda‐Tamai, Sachie, Ogawa, Haruko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443879/
https://www.ncbi.nlm.nih.gov/pubmed/30984549
http://dx.doi.org/10.1002/2211-5463.12616
Descripción
Sumario: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 (CCl(4)). 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 CCl(4)‐VN increased and the ratio of active molecules to collagen in plasma decreased. Increased fucosylation of LC‐VN was not detected in carbohydrates of CCl(4)‐VN. The changes in rat VN due to CCl(4) 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 CCl(4)‐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.