High expression of MDR1, MRP1, and MRP3 in the hepatic progenitor cell compartment and hepatocytes in severe human liver disease
High expression of MDR1, MRP1, and MRP3 in the hepatic progenitor cell compartment and hepatocytes in severe human liver disease
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DOI：
10.1002/path.1379
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发表时间：
2003-08-01
影响因子：
7.3
通讯作者：
Roskams, TAD
中科院分区：
文献类型：
--
作者：
Ros, JE;Libbrecht, L;Roskams, TAD
在各种人类肝病中可以观察到胆管结构的增加。这些结构含有肝脏的祖细胞室。由于三磷酸腺苷结合盒(ABC)转运体在肝脏疾病中可能具有细胞保护作用，我们对原发性胆汁性肝硬变(PBC)、慢性丙型肝炎病毒(HCV)感染、亚大规模细胞坏死和正常肝脏的人肝标本进行了免疫组织化学研究。用特异性抗体检测mdr1、mdr3、BSEP、MRP1、MRP2和MRP3的表达。构建稀释序列来确定临界染色水平，以估计上调因子。在正常肝脏中，肝细胞显示MDR3、BSEP和MRP2的小管染色。MDR1对肝细胞和胆管细胞的小管膜均有染色。NIRP3仅在胆管上皮细胞和小叶中心肝细胞呈低免疫反应。正常肝脏无MRP1表达，MDR3、BSEP和MRP2表达相对稳定。在PBC、丙型肝炎和次大面积坏死组中，MDR1、MRP1和NIRP3的表达水平升高。在次大面积坏死后免疫反应最强，剩余的肝细胞岛显示NIDR1和NIRP3强烈的管状染色。在汇管区和坏死区交界处再生胆管，NIDR1、MRP1和MRP3染色强烈。总之，在严重的人类肝病中，MDR1、MRP1和NIRP3在肝细胞中表达上调。在再生的人胆管中可以看到很强的mdr1、MRP1和MRP3反应性。版权所有(C)2003 John Wiley Sons，Ltd.
An increase in bile ductular structures is observed in diverse human liver diseases. These structures harbour the progenitor cell compartment of the liver. Since ATP-binding cassette (ABC) transporters may have a cytoprotective role in liver disease, an immunohistochemical study was performed on human liver specimens from patients with primary biliary cirrhosis (PBC), chronic hepatitis C virus (HCV) infection, submassive cell necrosis, and normal liver. The expression of MDR1, MDR3, BSEP, MRP1, MRP2, and MRP3 was determined using specific antibodies. Dilution series were constructed to determine the critical staining level in order to estimate the factor of up-regulation. In normal liver, hepatocytes showed canalicular staining for MDR3, BSEP, and MRP2. MDR1 stained the canalicular membrane of hepatocytes as well as that of cholangiocytes. NIRP3 showed low immunoreactivity of bile duct epithelial cells and centrilobular hepatocytes only. Normal liver showed no immunoreactivity for MRP1 In diseased liver, the expression of MDR3, BSEP, and MRP2 was relatively stable. In PBC, HCV, and submassive necrosis, the expression levels of MDR1, MRP1, and NIRP3 were increased. The strongest immunoreactivity was seen after submassive necrosis, where remaining islands of hepatocytes showed strong canalicular staining for NIDR1 and NIRP3. Regenerating bile ductules at the interface of portal tracts and necrotic areas stained intensely for NIDR1, MRP1, and MRP3. In conclusion, MDR1, MRP1, and NIRP3 are up-regulated in hepatocytes in severe human liver disease. Strong MDR1, MRP1, and MRP3 reactivity is seen in regenerating human bile ductules. Copyright (C) 2003 John Wiley Sons, Ltd.