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Published on: July 16, 2012
No evidence of the unfolded protein response in patients with chronic hepatitis C virus infection
Stuart McPherson1, Elizabeth E Powell, Helen D Barrie
1Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Insights
The unfolded protein response (UPR) is not activated in patients with chronic Hepatitis C virus (HCV) infection. This suggests the UPR may not significantly contribute to liver injury in chronic HCV.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Hepatitis C virus (HCV) proteins are known to activate the unfolded protein response (UPR) in experimental settings.
- The specific role of the UPR in the liver injury associated with chronic HCV infection remains unclear.
- This study aimed to elucidate the involvement of the UPR in the pathogenesis of chronic HCV.
Purpose of the Study:
- To investigate the activation status of the UPR in liver biopsy samples from patients with chronic HCV.
- To determine the correlation between UPR components and liver injury markers in chronic HCV.
Main Methods:
- Analysis of liver biopsy samples from 124 patients with chronic HCV and 24 healthy controls.
- Quantification of hepatic mRNA expression for UPR components using real-time PCR.
- Assessment of Glucose-regulated protein (GRP) 78 protein levels via immunohistochemistry.
Main Results:
- Significantly lower mRNA expression of GRP78 and growth arrest and damage inducible protein 34 (GADD34) was observed in HCV patients compared to controls.
- No significant differences were found in the expression of GRP94, spliced X-box binding protein 1 (sXBP1), C/EBP homologous protein (CHOP), EDEM mRNA, or GRP78 protein.
- No associations were identified between UPR elements and inflammation or fibrosis in the studied HCV cohort.
Conclusions:
- Downstream components of the UPR do not appear to be activated in individuals with chronic HCV infection.
- The UPR may not play a significant role in the liver injury observed in chronic HCV pathogenesis.
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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