Protective effect of SMAD-Specific E3 ubiquitin protein ligase 1 in alcoholic steatohepatitis in mice

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F19%3A00078487" target="_blank" >RIV/00023001:_____/19:00078487 - isvavai.cz</a>

Result on the web

<a href="https://aasldpubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep4.1427" target="_blank" >https://aasldpubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep4.1427</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/hep4.1427" target="_blank" >10.1002/hep4.1427</a>

Result language

angličtina

Original language name

Protective effect of SMAD-Specific E3 ubiquitin protein ligase 1 in alcoholic steatohepatitis in mice

Original language description

Excessive accumulation of lipids in the liver is crucial in the pathogenesis of alcoholic steatohepatitis and may be partly mediated by impaired degradation of lipid droplets by autophagy. The E3 ubiquitin ligase SMAD-specific E3 ubiquitin protein ligase 1 (SMURF1) regulates selective autophagy by ubiquitinating proteins on cargo destined for autophagic delivery to the lysosome for degradation. Here, we evaluated the role of SMURF1 in the regulation of hepatic lipid degradation in alcoholic steatohepatitis. In patients with severe alcoholic hepatitis, SMURF1 colocalized with lipid droplet membranes in liver explants. In a mouse model of alcoholic steatohepatitis, Smurf1(-/-) mice fed an alcohol diet displayed increased hepatocyte accumulation of lipid droplets and triglycerides as well as more severe liver injury compared to wild-type mice. The increased severity of liver steatosis in alcohol-fed Smurf1(-/-) mice was rescued by adeno-associated virus (AAV) serotype 8-mediated hepatic expression of wild-type Smurf1 protein but not by mutant Smurf1 proteins either lacking the catalytically active cysteine 699 required for ubiquitin transfer or the N-terminal C2 phospholipid membrane-binding domain. Conclusion: Smurf1 plays a protective role in the pathogenesis of alcoholic steatohepatitis through a mechanism that requires both its ubiquitin-ligase activity and C2 phospholipid-binding domains. These findings have implications for understanding the roles of ubiquitin ligases in fatty liver disease.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30219 - Gastroenterology and hepatology

Project

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Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Hepatology communications

ISSN

2471-254X

e-ISSN

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Volume of the periodical

3

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

1450-1458

UT code for WoS article

000486263000001

EID of the result in the Scopus database

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