Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
J Gastroenterol Hepatol. 2011 Feb;26(2):319-27. doi: 10.1111/j.1440-1746.2010.06368.x.
Hepatitis C virus (HCV) proteins activate the unfolded protein response (UPR) in experimental models. The role of the UPR in the pathogenesis of HCV-induced liver injury has not been determined. Our aim was to investigate the role of the UPR in the pathogenesis of chronic HCV.
Liver biopsy samples from 124 patients with chronic HCV and 24 HCV/HBV-negative subjects with histologically normal liver (NDL) were assessed. The hepatic mRNA expression of components of the UPR was measured by semi-quantitative real-time polymerase chain reaction. Glucose regulated protein (GRP) 78 protein expression was assessed by immunohistochemistry.
The expression of GRP78 mRNA and growth arrest and damage inducible protein 34 (GADD34) mRNA was significantly lower in subjects with HCV than NDL (P = 0.007 and P < 0.001, respectively). There was no significant difference in the expression of GRP94 mRNA, spliced X box binding protein 1 (sXBP1) mRNA, C/EBP homologous protein mRNA (CHOP) and ER degradation enhancing α-mannosidase-like protein (EDEM) mRNA and GRP78 protein between patients with HCV and NDL. There were no relationships between elements of the UPR and inflammation or fibrosis in patients with HCV.
Downstream components of UPR were not activated in patients with chronic HCV. Therefore, the UPR may not play a prominent role in liver injury in patients with chronic HCV infection.
丙型肝炎病毒（HCV）蛋白在实验模型中激活未折叠蛋白反应（UPR）。UPR 在 HCV 诱导的肝损伤发病机制中的作用尚未确定。我们的目的是研究 UPR 在慢性 HCV 发病机制中的作用。
评估了 124 例慢性 HCV 患者和 24 例 HCV/乙型肝炎病毒阴性组织学正常肝（NDL）患者的肝活检样本。通过半定量实时聚合酶链反应测量 UPR 成分的肝mRNA 表达。通过免疫组织化学评估葡萄糖调节蛋白（GRP）78 蛋白表达。
与 NDL 相比，HCV 患者的 GRP78mRNA 和生长停滞和 DNA 损伤诱导蛋白 34（GADD34）mRNA 的表达显着降低（P=0.007 和 P<0.001）。GRP94mRNA、剪接 X 盒结合蛋白 1（sXBP1）mRNA、C/EBP 同源蛋白 mRNA（CHOP）和 ER 降解增强 α-甘露糖苷酶样蛋白（EDEM）mRNA 和 GRP78 蛋白在 HCV 患者和 NDL 之间无显着差异。HCV 患者 UPR 的各个要素与炎症或纤维化之间均无关系。
慢性 HCV 患者的 UPR 下游成分未被激活。因此，UPR 可能在慢性 HCV 感染患者的肝损伤中不起主要作用。
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