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.
| Original language | English |
|---|---|
| Pages (from-to) | 1107-1115 |
| Number of pages | 9 |
| Journal | Proteomics |
| Volume | 14 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Biomedicine
- Hepatic iron overload
- Hepatitis C infection
- Liver fibrosis
- Vitronectin
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry
- Medicine(all)
Cite this
Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload. / Montaldo, Claudia; Mattei, Simone; Baiocchini, Andrea; Rotiroti, Nicolina; Nonno, Franca Del; Pucillo, Leopoldo Paolo; Cozzolino, Angela Maria; Battistelli, Cecilia; Amicone, Laura; Ippolito, Giuseppe; van Noort, Vera; Conigliaro, Alice; Alonzi, Tonino; Tripodi, Marco; Mancone, Carmine.
In: Proteomics, Vol. 14, No. 9, 2014, p. 1107-1115.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload
AU - Montaldo, Claudia
AU - Mattei, Simone
AU - Baiocchini, Andrea
AU - Rotiroti, Nicolina
AU - Nonno, Franca Del
AU - Pucillo, Leopoldo Paolo
AU - Cozzolino, Angela Maria
AU - Battistelli, Cecilia
AU - Amicone, Laura
AU - Ippolito, Giuseppe
AU - van Noort, Vera
AU - Conigliaro, Alice
AU - Alonzi, Tonino
AU - Tripodi, Marco
AU - Mancone, Carmine
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Biomedicine
KW - Hepatic iron overload
KW - Hepatitis C infection
KW - Liver fibrosis
KW - Vitronectin
UR - http://www.scopus.com/inward/record.url?scp=84898630514&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898630514&partnerID=8YFLogxK
U2 - 10.1002/pmic.201300422
DO - 10.1002/pmic.201300422
M3 - Article
C2 - 24616218
AN - SCOPUS:84898630514
VL - 14
SP - 1107
EP - 1115
JO - Proteomics
JF - Proteomics
SN - 1615-9853
IS - 9
ER -