title: PPARs and HCV-Related Hepatocarcinoma: A Mitochondrial Point of View.
abstract: Hepatitis-C-virus-related infective diseases are worldwide spread pathologies affecting primarily liver. The infection is often asymptomatic, but when chronically persisting can lead to liver scarring and ultimately to cirrhosis, which is generally apparent after decades. In some cases, cirrhosis will progress to develop liver failure, liver cancer, or life-threatening esophageal and gastric varices. HCV-infected cells undergo profound metabolic dysregulation whose mechanisms are yet not well understood. An emerging feature in the pathogenesis of the HCV-related disease is the setting of a pro-oxidative condition caused by dysfunctions of mitochondria which proved to be targets of viral proteins. This causes deregulation of mitochondria-dependent catabolic pathway including fatty acid oxidation. Nuclear receptors and their ligands are fundamental regulators of the liver metabolic homeostasis, which are disrupted following HCV infection. In this contest, specific attention has been focused on the peroxisome proliferator activated receptors given their role in controlling liver lipid metabolism and the availability of specific pharmacological drugs of potential therapeutic utilization. However, the reported role of PPARs in HCV infection provides conflicting results likely due to different species-specific contests. In this paper we summarize the current knowledge on this issue and offer a reconciling model based on mitochondria-related features.
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS, Centro di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture (Pz), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Agriesti
authors.forename: Tiziana
authors.initials: T
authors.lastname: Tataranni
authors.forename: Vitalba
authors.initials: V
authors.lastname: Ruggieri
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Capitanio
authors.forename: Claudia
authors.initials: C
authors.lastname: Piccoli