Agrin, a novel basement membrane component in human and rat liver, accumulates in cirrhosis and hepatocellular carcinoma
Agrin, a novel basement membrane component in human and rat liver, accumulates in cirrhosis and hepatocellular carcinoma
复制标题
Agrin 是人和大鼠肝脏中的一种新型基底膜成分，在肝硬化和肝细胞癌中积累
DOI：
10.1038/labinvest.3700475
复制
发表时间：
2006
影响因子：
5
通讯作者：
I. Kovalszky
中科院分区：
文献类型：
--
作者：
Péter Tátrai;J. Dudás;E. Batmunkh;M. Máthé;A. Zalatnai;Z. Schaff;G. Ramadori;I. Kovalszky
Agrin 是一种多功能硫酸乙酰肝素蛋白多糖，最初在神经肌肉接头中发现，后来在许多其他部位观察到。无论是健康的还是患病的肝脏中是否存在集聚蛋白，以前都没有报道过。我们在健康肝脏的血管和胆管的基底膜中检测到少量的集聚蛋白。肝硬化中胆管的增殖和新间隔血管的形成以及肝细胞癌（HCC）中的新血管生成导致集聚蛋白的数量急剧增加。在 29/29 的肝硬化和 HCC 人类肝脏样本中，血管和胆管周围基底膜的集聚蛋白呈强免疫阳性。然而，肝硬化肝中再生结节的窦壁始终保持阴性。鉴于集聚蛋白对肿瘤微血管的选择性，集聚蛋白免疫组织化学可能有助于识别肝硬化肝脏的恶性转化。对接受肝硬化/肝癌联合诱导治疗的大鼠的肝脏进行了类似的免疫组织化学观察。在人和大鼠中，集聚蛋白可能源自活化的肌成纤维细胞、血管平滑肌细胞和胆管上皮细胞。通过定量 RT-PCR 验证了人类标本、4/4 处理大鼠的肝脏以及分离的大鼠肝间充质细胞中集聚蛋白表达的增加。考虑到集聚蛋白结合各种生长因子，并且它直接与细胞膜受体（例如αv-整合素）相互作用，我们假设集聚蛋白在肿瘤血管形成等新血管生成过程中具有刺激作用，并且在胆管增殖中具有支持作用。
Agrin is a multifunctional heparan sulfate proteoglycan originally discovered in the neuromuscular junctions and later observed in numerous other localizations. The presence of agrin in the liver, either healthy or diseased, has formerly not been reported. We detected agrin in minor amounts in the basement membranes of blood vessels and bile ducts in the healthy liver. The proliferation of bile ductules and the formation of new septal blood vessels in liver cirrhosis, as well as neoangiogenesis in the hepatocellular carcinoma (HCC) result in a dramatic increase in the quantity of agrin. Vascular and peribiliary basement membranes were strongly immunopositive for agrin in 29/29 human liver specimens with cirrhosis and HCC. However, sinusoidal walls of regenerative nodules in the cirrhotic liver consistently remained negative. Given the selectivity of agrin for tumor microvessels, agrin immunohistochemistry may prove helpful in recognizing malignant transformation in cirrhotic livers. Similar immunohistochemical observations were made on the liver of rats exposed to a combined cirrhosis/HCC induction treatment. In both human and rats, agrin probably originates from activated myofibroblasts, vascular smooth muscle cells and biliary epithelial cells. Increased agrin expression in human specimens, in the liver of 4/4 treated rats, as well as in isolated rat liver mesenchymal cells was verified by quantitative RT-PCR. Considering that agrin binds various growth factors, and it directly interacts with cell membrane receptors such as αv-integrins, we hypothesize a stimulatory role for agrin in neoangiogenic processes such as tumor vascularization, and a supportive role in bile ductule proliferation.
影响因子：
3.5
作者：
M. J. Stanley;M. Stanley;R. Sanderson;R. Zera
通讯作者：
M. J. Stanley;M. Stanley;R. Sanderson;R. Zera
影响因子：
15.9
作者：
Eliceiri, BP;Cheresh, DA
通讯作者：
Cheresh, DA