Ezrin-Radixin-Moesin-Binding Phosphoprotein (EBP50), an Estrogen-Inducible Scaffold Protein, Contributes to Biliary Epithelial Cell Proliferation
Ezrin-Radixin-Moesin-Binding Phosphoprotein (EBP50), an Estrogen-Inducible Scaffold Protein, Contributes to Biliary Epithelial Cell Proliferation
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DOI：
10.2353/ajpath.2009.080079
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发表时间：
2009-03-01
影响因子：
6
通讯作者：
Housset, Chantal
中科院分区：
文献类型：
--
作者：
Fouassier, Laura;Rosenberg, Peter;Housset, Chantal
Ezrin-radixin-moesin-binding phosphoprotein 50（EBP 50）锚定并调节上皮细胞中的顶端膜蛋白。EBP 50可被雌激素诱导，并可能影响细胞增殖，尽管后者的功能尚不清楚。这项研究的目的是确定EBP 50是否与肝脏疾病中发生的小管反应有关。EBP 50的表达在正常人肝脏，在人胆管病（ic，囊性纤维化，原发性胆汁性肝硬化，原发性硬化性胆管炎），并在大鼠进行胆管结扎检查。EBP 50的调节雌激素及其对增殖的影响进行了评估，在这两个胆管结扎大鼠avid Mz-Cha-1人胆管上皮细胞。细胞分离物和免疫组织化学研究的分析表明，在正常人肝脏中，EBP 50在肝细胞的小管膜中表达，并且与ezrin和囊性纤维化跨膜传导调节剂一起在胆管细胞的顶端域中表达。在人胆管病和胆管结扎大鼠中，EBP 50重新分布到细胞质和细胞核。EBP 50经历了短暂的增加，在大鼠胆管结扎后，胆管细胞，而这种表达在卵巢切除大鼠下调。此外，在Mz-Cha-1细胞中，EBP 50在17 β-雌二醇的作用下发生上调和细胞内再分布，而其增殖被siRNA介导的EBP 50敲低所抑制。这些结果表明，EBP 50的表达和分布都受到雌激素的调节，并有助于胆管上皮细胞的增殖反应。(Am J Pathol 2009.174：869-880; DOI：10.2353/ajpath.2009.080079）
Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) anchors and regulates apical membrane proteins in epithelia. EBP50 is inducible by estrogen and may affect cell proliferation, although this latter function remains unclear. The goal of this study was to determine whether EBP50 was implicated in the ductular reaction that occurs in liver disease. EBP50 expression was examined in normal human liver, in human cholangiopathies (ic, cystic fibrosis, primary biliary cirrhosis, and primary sclerosing cholangitis), and in rats subjected to bile-duct ligation. The regulation of EBP50 by estrogens and its impact on proliferation were assessed in both bile duct-ligated rats avid Mz-Cha-1 human biliary epithelial cells. Analyses of cell isolates and Immunohistochemical studies showed that in normal human liver, EBP50 is expressed in the canalicular membranes of hepatocytes and, together with ezrin and cystic fibrosis transmembrane conductance regulator, in the apical domains of cholangiocytes. In both human cholangiopathies and bile duct-ligated rats, EBP50 was redistributed to the cytoplasmic and nuclear compartments. EBP50 underwent a transient increase in rat cholangiocytes after bile-duct ligation, whereas such expression was down-regulated in ovariectomized rats. In addition, in Mz-Cha-1 cells, EBP50 underwent upregulation and intracellular redistribution in response to 17 beta-estradiol, whereas its proliferation was inhibited by siRNA-mediated EBP50 knockdown. These results indicate that both the expression and distribution of EBP50 are regulated by estrogens and contribute to the proliferative response in biliary epithelia] cells. (Am J Pathol 2009.174:869-880; DOI: 10.2353/ajpath.2009.080079)