Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Nardo, AD; Grün, NG; Zeyda, M; Dumanic, M; Oberhuber, G; Rivelles, E; Helbich, TH; Markgraf, DF; Roden, M; Claudel, T; Trauner, M; Stulnig, TM.
Impact of osteopontin on the development of non-alcoholic liver disease and related hepatocellular carcinoma.
Liver Int. 2020; 40(7):1620-1633 Doi: 10.1111/liv.14464 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Co-Autor*innen der Med Uni Graz
Claudel Thierry
Sommer Nicole
Trauner Michael
Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Abstract:
Osteopontin, a multifunctional protein and inflammatory cytokine, is overexpressed in adipose tissue and liver in obesity and contributes to the induction of adipose tissue inflammation and non-alcoholic fatty liver (NAFL). Studies performed in both mice and humans also point to a potential role for OPN in malignant transformation and tumour growth. To fully understand the role of OPN on the development of NAFL-derived hepatocellular carcinoma (HCC), we applied a non-alcoholic steatohepatitis (NASH)-HCC mouse model on osteopontin-deficient (Spp1-/- ) mice analysing time points of NASH, fibrosis and HCC compared to wild-type mice. Two-day-old wild-type and Spp1-/- mice received a low-dose streptozotocin injection in order to induce diabetes, and were fed a high-fat diet starting from week 4. Different cohorts of mice of both genotypes were sacrificed at 8, 12 and 19 weeks of age to evaluate the NASH, fibrosis and HCC phenotypes respectively. Spp1-/- animals showed enhanced hepatic lipid accumulation and aggravated NASH, as also increased hepatocellular apoptosis and accelerated fibrosis. The worse steatotic and fibrotic phenotypes observed in Spp1-/- mice might be driven by enhanced hepatic fatty acid influx through CD36 overexpression and by a pathological accumulation of specific diacylglycerol species during NAFL. Lack of osteopontin lowered systemic inflammation, prevented HCC progression to less differentiated tumours and improved overall survival. Lack of osteopontin dissociates NASH-fibrosis severity from overall survival and HCC malignant transformation in NAFLD, and is therefore a putative therapeutic target only for advanced chronic liver disease. © 2020 The Authors. Liver International published by John Wiley & Sons Ltd.

Find related publications in this database (Keywords)
acute-on-chronic liver failure
fibrosis
lipoapoptosis
metabolic syndrome
non-alcoholic fatty liver
© Med Uni Graz • Impressum