Characterization and Proteome of Circulating Extracellular Vesicles as Potential Biomarkers for NASH.

Povero, Davide; Yamashita, Hirokazu; Ren, Wenhua; Subramanian, Mani G; Myers, Robert P; Eguchi, Akiko; Simonetto, Douglas A; Goodman, Zachary D; Harrison, Stephen A; Sanyal, Arun J; Bosch, Jaime; Feldstein, Ariel E (2020). Characterization and Proteome of Circulating Extracellular Vesicles as Potential Biomarkers for NASH. Hepatology communications, 4(9), pp. 1263-1278. Wiley 10.1002/hep4.1556

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Nonalcoholic fatty liver disease (NAFLD) is currently one of most common forms of chronic liver disease globally. NAFLD represents a wide spectrum of liver involvement from nonprogressive isolated steatosis to nonalcoholic steatohepatitis (NASH), characterized by liver necroinflammation and fibrosis and currently one of the top causes of end-stage liver disease and hepatocellular carcinoma. At present, there is a lack of effective treatments, and a central barrier to the development of therapies is the requirement for an invasive liver biopsy for diagnosis of NASH. Discovery of reliable, noninvasive biomarkers are urgently needed. In this study, we tested whether circulating extracellular vesicles (EVs), cell-derived small membrane-surrounded structures with a rich cargo of bioactive molecules, may serve as reliable noninvasive "liquid biopsies" for NASH diagnosis and assessment of disease severity. Total circulating EVs and hepatocyte-derived EVs were isolated by differential centrifugation and size-exclusion chromatography from serum samples of healthy individuals, patients with precirrhotic NASH, and patients with cirrhotic NASH. EVs were further characterized by flow cytometry, electron microscopy, western blotting, and dynamic light scattering assays before performing a proteomics analysis. Our findings suggest that levels of total and hepatocyte-derived EVs correlate with NASH clinical characteristics and disease severity. Additionally, using proteomics data, we developed understandable, powerful, and unique EV-based proteomic signatures for potential diagnosis of advanced NASH. Conclusion: Our study shows that the quantity and protein constituents of circulating EVs provide strong evidence for EV protein-based liquid biopsies for NAFLD/NASH diagnosis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

UniBE Contributor:

Bosch, Jaime

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2471-254X

Publisher:

Wiley

Language:

English

Submitter:

Rahel Fuhrer

Date Deposited:

11 Dec 2020 16:31

Last Modified:

11 Dec 2020 16:31

Publisher DOI:

10.1002/hep4.1556

PubMed ID:

32923831

BORIS DOI:

10.7892/boris.148192

URI:

https://boris.unibe.ch/id/eprint/148192

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