title: Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload.
abstract: Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighted the hepatocytic vitronectin expression as the most promising specific biomarker for iron-associated fibrogenesis in HCV infections. Next, the robustness of our in vitro findings was challenged in human liver biopsies by immunohistochemistry and yielded two major results: (i) hepatocytic vitronectin expression is associated to liver fibrogenesis in HCV-infected patients with iron overload; (ii) hepatic vitronectin expression was found to discriminate also the transition between mild to moderate fibrosis in HCV-infected patients without iron overload.
authors.affiliation: Department of Cellular Biotechnologies and Haematology, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy; "L. Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Montaldo
authors.forename: Simone
authors.initials: S
authors.lastname: Mattei
authors.forename: Andrea
authors.initials: A
authors.lastname: Baiocchini
authors.forename: Nicolina
authors.initials: N
authors.lastname: Rotiroti
authors.forename: Franca
authors.initials: F
authors.lastname: Del Nonno
authors.forename: Leopoldo Paolo
authors.initials: LP
authors.lastname: Pucillo
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Cozzolino
authors.forename: Cecilia
authors.initials: C
authors.lastname: Battistelli
authors.forename: Laura
authors.initials: L
authors.lastname: Amicone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
authors.forename: Vera
authors.initials: V
authors.lastname: van Noort
authors.forename: Alice
authors.initials: A
authors.lastname: Conigliaro
authors.forename: Tonino
authors.initials: T
authors.lastname: Alonzi
authors.forename: Marco
authors.initials: M
authors.lastname: Tripodi
authors.forename: Carmine
authors.initials: C
authors.lastname: Mancone
mesh_terms: D015415:Biomarkers / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D006526:Hepatitis C / Q000378:metabolism*; D006801:Humans; D019190:Iron Overload / Q000378:metabolism*; D007553:Isotope Labeling; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D040901:Proteomics; D015854:Up-Regulation; D019096:Vitronectin / Q000032:analysis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D019096:Vitronectin
keywords: Biomedicine; Hepatic iron overload; Hepatitis C infection; Liver fibrosis; Vitronectin