Blomme Bram, Van Steenkiste Christophe, Callewaert Nico, Van Vlierberghe Hans
Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium.
J Hepatol. 2009 Mar;50(3):592-603. doi: 10.1016/j.jhep.2008.12.010. Epub 2008 Dec 27.
Chronic liver diseases are a serious health problem worldwide. The current gold standard to assess structural liver damage is through a liver biopsy which has several disadvantages. A non-invasive, simple and non-expensive test to diagnose liver pathology would be highly desirable. Protein glycosylation has drawn the attention of many researchers in the search for an objective feature to achieve this goal. Glycosylation is a posttranslational modification of many secreted proteins and it has been known for decades that structural changes in the glycan structures of serum proteins are an indication for liver damage. The aim of this paper is to give an overview of this altered protein glycosylation in different etiologies of liver fibrosis / cirrhosis and hepatocellular carcinoma. Although individual liver diseases have their own specific markers, the same modifications seem to continuously reappear in all liver diseases: hyperfucosylation, increased branching and a bisecting N-acetylglucosamine. Analysis at mRNA and protein level of the corresponding glycosyltransferases confirm their altered status in liver pathology. The last part of this review deals with some recently developed glycomic techniques that could potentially be used in the diagnosis of liver pathology.
慢性肝病是全球范围内严重的健康问题。目前评估肝脏结构损伤的金标准是肝活检,但它存在诸多缺点。因此,非常需要一种非侵入性、简单且经济的检测方法来诊断肝脏病理状况。蛋白质糖基化已引起众多研究人员的关注,他们试图寻找一种客观特征来实现这一目标。糖基化是许多分泌蛋白的翻译后修饰,几十年来人们已知血清蛋白聚糖结构的变化是肝脏损伤的一个指标。本文旨在概述肝纤维化/肝硬化和肝细胞癌不同病因中这种改变的蛋白质糖基化情况。尽管个别肝脏疾病有其自身特定的标志物,但相同的修饰似乎在所有肝脏疾病中不断出现:高岩藻糖基化、分支增加和一个平分型N - 乙酰葡糖胺。对相应糖基转移酶的mRNA和蛋白质水平分析证实了它们在肝脏病理中的改变状态。本综述的最后一部分介绍了一些最近开发的糖组学技术,这些技术有可能用于肝脏病理的诊断。