Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection. - Archive ouverte HAL Access content directly
Journal Articles Gastroenterology Year : 2005

Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection.

Sébastien Dharancy
  • Function : Author
Mathilde Malapel
  • Function : Author
Gabriel Perlemuter
Tania Roskams
  • Function : Author
Yang Cheng
  • Function : Author
Laurent Dubuquoy
Philippe Podevin
  • Function : Author
Filoména Conti
  • Function : Author
Valérie Canva
  • Function : Author
David Philippe
  • Function : Author
Luc Gambiez
  • Function : Author
Philippe Mathurin
  • Function : Author
Jean-Claude Paris
  • Function : Author
Yvon Calmus
  • Function : Author
Stanislas Pol
Pierre Desreumaux
  • Function : Author

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.
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Dates and versions

hal-00187509 , version 1 (14-11-2007)

Identifiers

  • HAL Id : hal-00187509 , version 1
  • PUBMED : 15685545

Cite

Sébastien Dharancy, Mathilde Malapel, Gabriel Perlemuter, Tania Roskams, Yang Cheng, et al.. Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection.. Gastroenterology, 2005, 128 (2), pp.334-42. ⟨hal-00187509⟩
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