Cholestasis in a rat model of graft-versus-host disease is accompanied by alteration of the expression and distribution of tight-junction-associated proteins.
Cholestasis in a rat model of graft-versus-host disease is accompanied by alteration of the expression and distribution of tight-junction-associated proteins.
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DOI：
10.3892/ijmm.15.3.431
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发表时间：
2005-03
影响因子：
5.4
通讯作者：
K. Sasatomi;S. Sakisaka;T. Kawaguchi;S. Hanada;E. Taniguchi;H. Koga;M. Harada;M. Sata
中科院分区：
文献类型：
--
作者：
K. Sasatomi;S. Sakisaka;T. Kawaguchi;S. Hanada;E. Taniguchi;H. Koga;M. Harada;M. Sata
肝内胆汁淤积是移植物抗宿主病（GVHD）的特征性肝脏表现之一。紧密连接（TJs）在肝细胞和/或胆管上皮细胞（BEC）中胆汁形成和TJs改变中起关键作用，所述TJs改变引起肝内胆汁淤积。为了评估大鼠GVHD模型中肝细胞和BEC中TJ的变化，我们检测了TJ相关蛋白7 H6和闭合小带（ZO）-1的定位。通过将亲本品系大鼠（Brown Norway）的脾细胞注射到未照射的（Brown Norway x刘易斯）F1杂种大鼠中来诱导GVHD。未处理的F1杂种大鼠作为对照。在肝脏切片中进行7 H6和ZO-1的双标记免疫荧光染色。在对照组大鼠中，7 H6和ZO-1的免疫染色共定位于BEC的顶端部位，并沿沿着胆小管连续。在GVHD中，7 H6在BEC中的表达减少，并且沿沿着胆小管是不连续的。另一方面，ZO-1在肝细胞中的染色强度增加，而在BEC中与对照大鼠相比没有变化。肝细胞和BEC TJ相关蛋白的变化可能反映了GVHD相关肝内胆汁淤积的免疫发病机制。
Intrahepatic cholestasis has been recognized as one of the characteristic features of the hepatic manifestations in graft-versus-host disease (GVHD). Tight junctions (TJs) play crucial roles in bile formation and alterations of TJs in hepatocytes and/or biliary epithelial cells (BECs) that cause intrahepatic cholestasis. To assess the changes of TJs in hepatocytes and BECs in a rat model of GVHD, we examined the localization of TJ-associated proteins, 7H6 and zonula occludens (ZO)-1. GVHD was induced by injecting spleen cells of parental strain rats (Brown Norway) into non-irradiated (Brown Norway x Lewis) F1 hybrid rats. Untreated F1 hybrid rats served as controls. Double-labeled immunofluorescent staining for 7H6 and ZO-1 was performed in liver sections. In control rats, immunostaining for 7H6 and ZO-1 colocalized to the apical site of BECs and was continuous along the bile canaliculi. In GVHD, 7H6 expression was decreased in BECs and was discontinuous along the bile canaliculi. On the other hand, the intensity of ZO-1 staining in hepatocytes increased and did not change in BECs compared with that of control rats. Changes in TJ-associated proteins of both hepatocytes and BECs may reflect the immunopathogenesis of GVHD-associated intrahepatic cholestasis.