No evidence of the unfolded protein response in patients with chronic hepatitis C virus infection

Authors

  • Stuart McPherson,

    1. Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
    2. School of Medicine, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia
    3. University of Newcastle, Newcastle, UK
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  • Elizabeth E Powell,

    1. Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
    2. School of Medicine, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia
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  • Helen D. Barrie,

    1. School of Medicine, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia
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  • Andrew D Clouston,

    1. School of Medicine, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia
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  • Michael McGuckin,

    1. Mucosal Diseases Program, Mater Medical Research Institute and the University of Queensland, Mater Health Services, South Brisbane, Queensland, Australia
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  • Julie R Jonsson

    Corresponding author
    1. School of Medicine, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia
      Associate Professor Julie Jonsson, School of Medicine, University of Queensland, Level 3, R Wing, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Qld 4102, Australia. Email: j.jonsson@uq.edu.au
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  • Statement of interests: This study was funded by the National Health and Medical Research Council of Australia, The Queensland Government's Smart State Health and Medical Research Fund, The Princess Alexandra Hospital Research and Development Foundation and The Sasakawa Foundation (Royal Children's Hospital, Brisbane). Elizabeth Powell was the recipient of an Unrestricted Education Grant from Schering-Plough.

Associate Professor Julie Jonsson, School of Medicine, University of Queensland, Level 3, R Wing, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Qld 4102, Australia. Email: j.jonsson@uq.edu.au

Abstract

Background and Aim:  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.

Methods:  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.

Results:  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.

Conclusion:  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.

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