Impact of osteopontin on the development of non‐alcoholic liver disease and related hepatocellular carcinoma

Nardo Alexander D.; Grün Nicole G.; Zeyda MaximilianDumanic MonikaOberhuber GeorgRivelles ElisaHelbich Thomas H.Markgraf Daniel F.Roden MichaelClaudel ThierryTrauner MichaelStulnig Thomas M.

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Impact of osteopontin on the development of non‐alcoholic liver disease and related hepatocellular carcinoma

机译：Impact of osteopontin on the development of non‐alcoholic liver disease and related hepatocellular carcinoma

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Abstract Background & aims 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. Methods 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. Results 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. Conclusions 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.

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《Liver international》 |2020年第7期|1620-1633|共14页
作者
Nardo Alexander D.; Grün Nicole G.; Zeyda MaximilianDumanic MonikaOberhuber GeorgRivelles ElisaHelbich Thomas H.Markgraf Daniel F.Roden MichaelClaudel ThierryTrauner MichaelStulnig Thomas M.;
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作者单位

Christian Doppler Laboratory for Cardio‐Metabolic Immunotherapy and Clinical Division of;

Division of Nuclear MedicineMedical University of ViennaVienna,Austria;

Department of PathologyGeneral Hospital of InnsbruckInnsbruck,AustriaDepartment of Laboratory MedicineMedical University of ViennaVienna,AustriaGerman Diabetes CenterInstitute for Clinical DiabetologyDüsseldorf,GermanyHans Popper Laboratory of Molecular HepatologyMedical University of ViennaVienna,Austria;

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正文语种英语
中图分类内科学;
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acute‐on‐chronic liver failure; fibrosis; lipoapoptosis; metabolic syndrome; non‐alcoholic fatty liver;

Impact of osteopontin on the development of non‐alcoholic liver disease and related hepatocellular carcinoma

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