Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload

Autor: Leopoldo Paolo Pucillo, Andrea Baiocchini, Carmine Mancone, Franca Del Nonno, Marco Tripodi, Vera van Noort, Tonino Alonzi, Claudia Montaldo, Nicolina Rotiroti, Giuseppe Ippolito, Laura Amicone, Alice Conigliaro, Angela Maria Cozzolino, Cecilia Battistelli, Simone Mattei
Přispěvatelé: Montaldo, C., Mattei, S., Baiocchini, A., Rotiroti, N., Nonno, F., Pucillo, L., Cozzolino, A., Battistelli, C., Amicone, L., Ippolito, G., van Noort, V., Conigliaro, A., Alonzi, T., Tripodi, M., Mancone, C., Department of Cellular Biotechnologies and Haematology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), L. Spallanzani, National Institute for Infectious Diseases (IRCCS), European Molecular Biology Laboratory [Heidelberg] (EMBL), This work was supported by grants from MIUR Ministero dell’Universit `a e Ricerca Scientifica (FIRB 2012, codice progetto RBFR12NSCF), Associazione Italiana per la Ricerca sul Cancro (AIRC) andMinistero della Salute (Ricerca Finalizzata 40H27, Ricerca Corrente).
Rok vydání: 2014
Předmět:
Liver Cirrhosis
Proteomics
hepatitis C virus
Male
MESH: Isotope Labeling
HSC
medicine.disease_cause
Biochemistry
0302 clinical medicine
Fibrosis
MESH: Up-Regulation
Membrane Protein
hepatic stellate cell
liver fibrosis
hepatic iron overload
0303 health sciences
biology
MESH: Proteomics
Medicine (all)
hepatocellular carcinoma
Biomedicine
hepatitis c infection
vitronectin
Hepatitis C
[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
Up-Regulation
3. Good health
cell culture-derived HCV
Isotope Labeling
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Hepatic iron overload
Hepatitis C infection
Liver fibrosis
Vitronectin
Biomarkers
Cell Line
Humans
Iron Overload
Membrane Proteins
Molecular Biology
HCV
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Biomarker (medicine)
MESH: Membrane Proteins
MESH: Liver Cirrhosis
Human
Liver Cirrhosi
Hepatitis C virus
MESH: Iron Overload
03 medical and health sciences
medicine
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
030304 developmental biology
MESH: Hepatitis C
MESH: Humans
MESH: Biological Markers
Liver fibrosi
Proteomic
Biomarker
medicine.disease
MESH: Vitronectin
MESH: Male
digestive system diseases
MESH: Cell Line
Biomedicine / Abbreviations: HCC
HCVcc
Immunology
Cancer research
Hepatic stellate cell
biology.protein
Steatosis
Zdroj: Proteomics
Proteomics, Wiley-VCH Verlag, 2014, 14 (9), pp.1107-15. ⟨10.1002/pmic.201300422⟩
ISSN: 1615-9853
1615-9861
DOI: 10.1002/pmic.201300422
Popis: 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.
Databáze: OpenAIRE
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