Hepatitis C Virus Receptors Claudin-1 and Occludin After Liver Transplantation and Influence on Early Viral Kinetics
Hepatitis C Virus Receptors Claudin-1 and Occludin After Liver Transplantation and Influence on Early Viral Kinetics
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DOI：
10.1002/hep.24110
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发表时间：
2011-05-01
期刊：
影响因子：
13.5
通讯作者：
Forns, Xavier
中科院分区：
文献类型：
--
作者：
Mensa, Laura;Crespo, Gonzalo;Forns, Xavier
肝移植（LT）是研究丙型肝炎病毒（HCV）进入肝细胞的独特模型。最近的体外研究表明，HCV感染后，HCV受体claudin-1和occludin的表达发生了显着变化。我们的目标是：（1）表征来自LT受体的移植物中claudin-1和occludin的表达;（2）探索它们对早期HCV动力学的潜在影响以及它们在HCV感染后的变化。我们纳入了42名HCV感染的LT接受者和19名未感染的对照。Claudin-1和occludin检测石蜡包埋的肝活检组织中获得的再灌注和3个月和12个月后LT。HCV受体的特点是通过共聚焦免疫荧光显微镜，定量和共定位研究进行了专用软件。Claudin-1和occludin的表达仅限于肝细胞的顶端。肝移植术后24小时内HCV-RNA的降解与再灌注时清道夫受体B1的含量呈显著相关（r = 5 0.5 5，P = 5 0.0 0 7）。肝移植术后1周内，HCV-RNA上升斜率与claudin和occludin水平呈显著正相关（r = 50.63，P = 50.005）。移植术后12个月，Occludin和claudin-1水平显著升高（分别为P = 5 0.03和P = 5 0.007）。然而，这两种蛋白的表达模式保持不变，强烈共定位（60%-94%）在肝细胞的顶膜。结论.肝移植时的HCV受体水平似乎可以调节早期的HCV动力学。肝移植后丙型肝炎复发与肝细胞膜中claudin-1和occludin水平升高有关，尽管它并没有改变它们在紧密连接中的定位。（肝脏学2011;53：1436-1445）
Liver transplantation (LT) is a unique model to study hepatitis C virus (HCV) entry into hepatocytes. Recent in vitro studies suggest significant changes in the expression of the HCV receptors claudin-1 and occludin after HCV infection. Our aims were: (1) to characterize claudin-1 and occludin expression in grafts from LT recipients and (2) to explore their potential influence on early HCV kinetics and their changes after HCV infection. We included 42 HCV-infected LT recipients and 19 uninfected controls. Claudin-1 and occludin were detected in paraffin-embedded liver biopsies obtained during reperfusion and 3 and 12 months after LT. HCV receptors were characterized by confocal immunofluorescence microscopy; quantification and colocalization studies were performed with dedicated software. Claudin-1 and occludin expression were restricted to the apical pole of hepatocytes. There was a significant correlation between the amount of scavenger receptor B1 at the time of reperfusion and the HCV-RNA decay during the first 24 hours following LT (r = 5 0.55, P = 5 0.007). Similarly, there was a significant correlation between the levels of claudin and occludin and the slope of HCV-RNA increase during the first week after LT (r = 5 0.63, P = 5 0.005). Occludin and claudin-1 levels increased significantly 12 months after LT (P = 5 0.03 and P = 5 0.007, respectively). The expression pattern of both proteins, however, remained unchanged, colocalizing strongly (60%-94%) at the apical membrane of hepatocytes. Conclusions. HCV receptor levels at the time of LT seem to modulate early HCV kinetics. Hepatitis C recurrence after LT was associated with increased levels of claudin-1 and occludin in the hepatocyte cell membrane, although it did not alter their localization within the tight junctions. (HEPATOLOGY 2011;53:1436-1445)