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Spike‐in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload
Author(s) -
Montaldo Claudia,
Mattei Simone,
Baiocchini Andrea,
Rotiroti Nicolina,
no Franca Del,
Pucillo Leopoldo Paolo,
Cozzolino Angela Maria,
Battistelli Cecilia,
Amicone Laura,
Ippolito Giuseppe,
Noort Vera,
Conigliaro Alice,
Alonzi Tonino,
Tripodi Marco,
Mancone Carmine
Publication year - 2014
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201300422
Subject(s) - vitronectin , stable isotope labeling by amino acids in cell culture , fibrosis , hepatitis c virus , hepatocellular carcinoma , steatosis , pathology , biology , immunology , cancer research , medicine , proteomics , cell , virus , fibronectin , biochemistry , endocrinology , gene
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 S pike‐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.