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RESEARCH PRODUCT
Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload
Leopoldo Paolo PucilloAndrea BaiocchiniCarmine ManconeFranca Del NonnoMarco TripodiVera Van NoortTonino AlonziClaudia MontaldoNicolina RotirotiGiuseppe IppolitoLaura AmiconeAlice ConigliaroAngela Maria CozzolinoCecilia BattistelliSimone Matteisubject
Liver CirrhosisProteomicshepatitis C virusMaleMESH: Isotope LabelingHSCmedicine.disease_causeBiochemistry0302 clinical medicineFibrosisMESH: Up-RegulationMembrane Proteinhepatic stellate cellliver fibrosishepatic iron overload0303 health sciencesbiologyMESH: ProteomicsMedicine (all)hepatocellular carcinomaBiomedicine; hepatitis c infection; liver fibrosis; hepatic iron overload; vitronectinHepatitis C[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]Hepatitis CUp-Regulation3. Good healthcell culture-derived HCVIsotope Labeling030220 oncology & carcinogenesisHepatocellular carcinomaBiomedicine; Hepatic iron overload; Hepatitis C infection; Liver fibrosis; Vitronectin; Biomarkers; Cell Line; Hepatitis C; Humans; Iron Overload; Isotope Labeling; Liver Cirrhosis; Male; Membrane Proteins; Proteomics; Up-Regulation; Vitronectin; Molecular Biology; Biochemistry; Medicine (all)HCV[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/VirologyBiomarker (medicine)VitronectinMESH: Membrane ProteinsMESH: Liver CirrhosisHumanIron OverloadLiver CirrhosiHepatitis C virusvitronectinhepatitis c infectionCell LineMESH: Iron Overload03 medical and health sciencesmedicineHumans[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyMolecular Biology030304 developmental biologyMESH: Hepatitis CMESH: HumansMESH: Biological MarkersMembrane ProteinsLiver fibrosiProteomicBiomarkermedicine.diseaseMESH: VitronectinMESH: Maledigestive system diseasesMESH: Cell LineBiomedicineBiomedicine / Abbreviations: HCCHCVccImmunologyCancer researchHepatic stellate cellbiology.proteinSteatosisBiomarkersdescription
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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-05-01 | PROTEOMICS |