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Int. J. Mol. Sci. 2018, 19(2), 603; https://doi.org/10.3390/ijms19020603

Overexpression of the Vitronectin V10 Subunit in Patients with Nonalcoholic Steatohepatitis: Implications for Noninvasive Diagnosis of NASH

1
Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
2
Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Via Borelli 50, 00161 Rome, Italy
3
Department of Movement, Human and Health Sciences, Division of Health Sciences, University of Rome “Foro Italico”, Piazza Lauro De Bosis 6, 00135 Rome, Italy
4
Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
5
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 30 January 2018 / Revised: 13 February 2018 / Accepted: 16 February 2018 / Published: 18 February 2018
(This article belongs to the Special Issue Extracellular Matrix in Development and Disease)
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Abstract

Nonalcoholic steatohepatitis (NASH) is the critical stage of nonalcoholic fatty liver disease (NAFLD). The persistence of necroinflammatory lesions and fibrogenesis in NASH is the leading cause of liver cirrhosis and, ultimately, hepatocellular carcinoma. To date, the histological examination of liver biopsies, albeit invasive, remains the means to distinguish NASH from simple steatosis (NAFL). Therefore, a noninvasive diagnosis by serum biomarkers is eagerly needed. Here, by a proteomic approach, we analysed the soluble low-molecular-weight protein fragments flushed out from the liver tissue of NAFL and NASH patients. On the basis of the assumption that steatohepatitis leads to the remodelling of the liver extracellular matrix (ECM), NASH-specific fragments were in silico analysed for their involvement in the ECM molecular composition. The 10 kDa C-terminal fragment of the ECM protein vitronectin (VTN) was then selected as a promising circulating biomarker in discriminating NASH. The analysis of sera of patients provided these major findings: the circulating VTN fragment (i) is overexpressed in NASH patients and positively correlates with the NASH activity score (NAS); (ii) originates from the disulfide bond reduction between the V10 and the V65 subunits. In conclusion, V10 determination in the serum could represent a reliable tool for the noninvasive discrimination of NASH from simple steatosis. View Full-Text
Keywords: nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; liver fibrosis; secretome nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; liver fibrosis; secretome
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Del Ben, M.; Overi, D.; Polimeni, L.; Carpino, G.; Labbadia, G.; Baratta, F.; Pastori, D.; Noce, V.; Gaudio, E.; Angelico, F.; Mancone, C. Overexpression of the Vitronectin V10 Subunit in Patients with Nonalcoholic Steatohepatitis: Implications for Noninvasive Diagnosis of NASH. Int. J. Mol. Sci. 2018, 19, 603.

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