Perlecan和alpha-dystroglycan在肝硬化病患跟正常人中的表現差異

慢性病毒的肝炎可能導致肝臟硬化，並且肝硬化的併發症可能導致肝臟受到更大的傷害進而危害到生命。因此，儘早對肝臟纖維化和肝硬化診斷是相當重要的。目前臨床上評估肝臟纖維化嚴重程度的黃金指標是利用肝生檢，但是肝生檢這個方式是侵入性的檢驗會有潛藏併發症的可能且費用昂貴。所以，我們希望能夠用檢測血清中perlecan 和 alpha-dystroglycan 這兩個醣蛋白質在肝硬化病患及非肝硬化的正常人中找出不同處。 Dystroglycan 和 perlecan是細胞外間質的成分之一。 Perlecan這個醣蛋白質是屬於醣胺聚多醣（glycosaminoglycan, GAG），而醣胺聚多醣會和細胞表面上的proteoglycan 連結，因此當細胞發生改變時也會造成醣胺聚多醣結構上產生變化。Heparan sulfate proteoglycans（ HSPGs ）藉由調停對引起絲狀分裂的和血管原的生長因素的黏附和遷移反應在腫瘤生物中扮演不同的角色。而dystroglycan 可分為兩部份分別為α-dystroglycan 和β-dystroglycan ，α-dystroglycan 的分子量約120-180 kDa 在細胞膜外部會和其他蛋白質結合，β-dystroglycan則為 43 kDa連接在細胞膜上，因為dystroglycan 與一些肌肉疾病的發生有關。Dystroglycan（DG） , 是一個non-integrin 黏附分子，是組成dystrophin-glycoprotein 複合物關鍵性的成分，而這個複合物常表現在基底膜和細胞膜之間。當改變肝臟的細胞外間質時可能會造成肝臟纖維化，最近的研究也指出 perlecan 和 dystroglycan的表現時常被發現在人類的癌症中。我們用lectin blot去觀察醣的表現在以 perlecan和alpha-dystroglycan 為抗體進行蛋白質免疫沉澱的肝硬化患者和非肝硬化正常人的血清樣本，我們從統計圖中發現病人和正常人並無明顯之差異。

關鍵字

肝硬化； proteoglycan ； heparan sulfate ； perlecan ； dystroglycan

並列摘要

Chronic viral hepatitis may lead to liver cirrhosis, and complications of liver cirrhosis may cause substantial morbidity and mortality. It is important to have early diagnosis for liver fibrosis and cirrhosis. Liver biopsy is the gold standard for the evaluation of hepatic fibrosis. The current diagnosis method has high risk. And, it is too expansive. Therefore, we have investigated into the expression of serum perlecan and α-dystroglycan in normal with liver disease free and patients with liver cirrhosis. Perlecan is a ubiquitous heparin sulfate proteoglycan that is an intrinsic constituent of all basement membranes and extracellular matrices. The heparan sulfate proteoglycans （HSPGs）play diverse roles in tumor biology by mediating adhesion and migration and cellular responses to mitogenic and angiogenic growth factors. Dystroglycan (DG), a non-integrin adhesion molecule, is a pivotal component of the dystrophin-glycoprotein complex that is expressed in skeletal muscle and in a wide variety of tissues, at the interface between the basement membrane (BM) and the cell membrane. Dystroglycan and perlecan are one of the extracellular matrix（ECM） components. Changes of ECM components may cause liver fibrosis. Recent studies also indicate that abnormalities in the expression of perlecan and DG frequently occur in human cancers and may play a role in both the process of tumor progression and in the maintenance of the malignant phenotype. We have used lectin blot to observe glycan expression of immunoprecipitated perlecan and dystroglycan from serum of liver cirrhosis patients and normal human with liver disease free as healthy control. But there is no difference between the serum samples from the patients with liver cirrhosis patients and healthy controls.

並列關鍵字

liver cirrhosis ； heparan sulfate ； proteoglycan ； perlecan ； dystroglycan

參考文獻

1. Snow, A.D., Kinsella, M. G., Parks, E., Sekiguchi, R. T., Miller, J. D., Kimata, K., Wight, T. N., Differential binding of vascular cell-derived proteoglycans (perlecan, biglycan, decorin, and versican) to the beta-amyloid protein of Alzheimer's disease. Arch Biochem Biophys, 1995. 320(1): p. 84-95.

2. Gallai, M., Sebestyen, A., Nagy, P., Kovalszky, I., Onody, T., Thorgeirsson, S. S., Proteoglycan gene expression in rat liver after partial hepatectomy. Biochem Biophys Res Commun, 1996. 228(3): p. 690-4.

3. Laplante, P., Raymond, M. A., Gagnon, G., Vigneault, N., Sasseville, A. M., Langelier, Y., Bernard, M., Raymond, Y., Hebert, M. J., Novel fibrogenic pathways are activated in response to endothelial apoptosis: implications in the pathophysiology of systemic sclerosis. J Immunol, 2005. 174(9): p. 5740-9.

4. Kovalszky, I.I., Nagy, J. O., Gallai, M., Sebestyen, A., Schaff, Z., Paku, S., Jeney, A., Iozzo, R. V., Altered Proteoglycan Gene Expression in Human Biliary Cirrhosis. Pathol Oncol Res, 1997. 3(1): p. 51-58.

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Perlecan和alpha-dystroglycan在肝硬化病患跟正常人中的表現差異

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