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

International Journal of Molecular Sciences
Maria Del BenCarmine Mancone

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 ...Continue Reading

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Citations

Jan 11, 2019·International Journal of Molecular Sciences·Julia Thom OxfordMakenna J Hardy
Mar 20, 2019·International Journal of Experimental Pathology·Momoka HayashidaYasunori Miyamoto

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Methods Mentioned

BETA
biopsies
biopsy
electrophoresis

Software Mentioned

MASCOT
Proteinpilot
ImageLab
SPSS
4000
4000 Series Explorer
Series Explorer

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