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Title: Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection
Authors: Dharancy, Sébastien ×
Malapel, Mathilde
Perlemuter, Gabriel
Roskams, Tania
Cheng, Yang
Dubuquoy, Laurent
Podevin, Philippe
Conti, Filoména
Canva, Valérie
Philippe, David
Gambiez, Luc
Mathurin, Philippe
Paris, Jean-Claude
Schoonjans, Kristina
Calmus, Yvon
Pol, Stanislas
Auwerx, Johan
Desreumaux, Pierre #
Issue Date: Feb-2005
Series Title: Gastroenterology vol:128 issue:2 pages:334-42
Abstract: BACKGROUND AND AIMS: Liver inflammation, fibrosis, and dyslipidemia are common features in patients with chronic hepatitis C virus (HCV) infection. Because peroxisome proliferator-activated receptor alpha (PPARalpha) is highly expressed in the liver and is involved in the regulation of lipid metabolism and inflammation, we sought to determine whether HCV infection may locally impair PPARalpha expression and activity. METHODS: PPARalpha expression was investigated in liver biopsy specimens of 86 untreated patients with HCV infection and controls, by using real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. PPARalpha activity was assessed by quantification of the key gene target carnitine palmitoyl acyl-CoA transferase 1 (CPT1A) messenger RNA (mRNA).The influence of HCV core protein on PPARalpha mRNA expression was analyzed in vitro by real-time PCR in HCV core-expressing HepG2 cells activated with the PPARalpha ligand fenofibric acid. RESULTS: Hepatic concentrations of PPARalpha and CPT1A expressed by hepatocytes were impaired profoundly in the livers of untreated patients with HCV infection compared with controls. A mean decrease of 85% in PPARalpha mRNA expression paralleled with a lack of CPT1A mRNA induction also were observed in HCV core-expressing HepG2 cells compared with controls. CONCLUSIONS: HCV infection is related to altered expression and function of the anti-inflammatory nuclear receptor PPARalpha. These results identify hepatic PPARalpha as one mechanism underlying the pathogenesis of HCV infection, and as a new therapeutic target in traditional treatment of HCV-induced liver injury.
URI: 
ISSN: 0016-5085
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
× corresponding author
# (joint) last author

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