title: HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2.
abstract: Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis.
authors.affiliation: Dept. of Experimental medicine, Sapienza University of Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Granato
authors.affiliation: Dept. of Molecular medicine, Sapienza University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Zompetta
authors.affiliation: Dept. of Experimental medicine, Sapienza University of Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Vescarelli
authors.affiliation: Dept. of Experimental medicine, Sapienza University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rizzello
authors.affiliation: Dept. of Experimental medicine, Sapienza University of Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cardi
authors.affiliation: Dept. of Molecular medicine, Sapienza University of Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Valia
authors.affiliation: Dept. of Molecular medicine, Sapienza University of Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Antonelli
authors.affiliation: Dept. of Experimental medicine, Sapienza University of Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Marchese
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti; Dept. Clinical and Molecular Medicine, Sapienza University of Rome, Italy.|Azienda Ospedaliera Sant' Andrea, Rome, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Torrisi
authors.affiliation: Dept. of Experimental medicine, Sapienza University of Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Faggioni
authors.affiliation: Dept. of Experimental medicine, Sapienza University of Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cirone
mesh_terms: D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000821:virology*; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000302:isolation & purification / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting; D009687:Nuclear Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000075746:Zinc Finger Protein Gli2 / Q000378:metabolism*
chemical_list: C082593:GLI2 protein, human; D009687:Nuclear Proteins; D000075746:Zinc Finger Protein Gli2