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

McPherson, Stuart, Powell, Elizabeth E., Barrie, Helen D., Clouston, Andrew D., McGuckin, Michael and Jonsson, Julie R. (2011) No evidence of the unfolded protein response in patients with chronic hepatitis C virus infection. Journal of Gastroenterology and Hepatalogy, 26 2: 319-327. doi:10.1111/j.1440-1746.2010.06368.x


Author McPherson, Stuart
Powell, Elizabeth E.
Barrie, Helen D.
Clouston, Andrew D.
McGuckin, Michael
Jonsson, Julie R.
Title No evidence of the unfolded protein response in patients with chronic hepatitis C virus infection
Journal name Journal of Gastroenterology and Hepatalogy   Check publisher's open access policy
ISSN 0815-9319
1440-1746
Publication date 2011-02
Year available 2010
Sub-type Article (original research)
DOI 10.1111/j.1440-1746.2010.06368.x
Volume 26
Issue 2
Start page 319
End page 327
Total pages 9
Place of publication Richmond, Vic., Australia
Publisher Wiley-Blackwell Publishing Asia
Collection year 2011
Language eng
Formatted 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.
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.
Keyword Endoplasmic reticulum stress
Fibrosis
Glucose regulated protein
Hepatitis C
Inflammation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 14 MAY 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Fri, 25 Feb 2011, 14:39:09 EST by Debbie Banks on behalf of School of Medicine