Hepatocyte apoptosis is tumor promoting in murine nonalcoholic steatohepatitis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62156489%3A43210%2F20%3A43917516" target="_blank" >RIV/62156489:43210/20:43917516 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/20:10408391
Result on the web
<a href="https://doi.org/10.1038/s41419-020-2283-9" target="_blank" >https://doi.org/10.1038/s41419-020-2283-9</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41419-020-2283-9" target="_blank" >10.1038/s41419-020-2283-9</a>
Alternative languages
Result language
angličtina
Original language name
Hepatocyte apoptosis is tumor promoting in murine nonalcoholic steatohepatitis
Original language description
Nonalcoholic fatty liver disease is the most common chronic liver disease and may progress to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). The molecular determinants of this pathogenic progression, however, remain largely undefined. Since liver tumorigenesis is driven by apoptosis, we examined the effect of overt hepatocyte apoptosis in a mouse model of NASH using mice lacking myeloid cell leukemia 1 (Mcl1), a pro-survival member of the BCL-2 protein family. Hepatocyte-specific Mcl1 knockout (Mcl1(hep)) mice and control littermates were fed chow or FFC (high saturated fat, fructose, and cholesterol) diet, which induces NASH, for 4 and 10 months. Thereafter, liver injury, inflammation, fibrosis, and tumor development were evaluated biochemically and histologically. Mcl1(hep) mice fed with the FFC diet for 4 months displayed a marked increase in liver injury, hepatocyte apoptosis, hepatocyte proliferation, macrophage-associated liver inflammation, and pericellular fibrosis in contrast to chow-fed Mcl1(hep) and FFC diet-fed Mcl1-expressing littermates. After 10 months of feeding, 78% of FFC diet-fed Mcl1(hep) mice developed liver tumors compared to 38% of chow-fed mice of the same genotype. Tumors in FFC diet-fed Mcl1(hep) mice were characterized by cytologic atypia, altered liver architecture, immunopositivity for glutamine synthetase, and histologically qualified as HCC. In conclusion, this study provides evidence that excessive hepatocyte apoptosis exacerbates the NASH phenotype with enhancement of tumorigenesis in mice.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cell Death & Disease
ISSN
2041-4889
e-ISSN
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Volume of the periodical
11
Issue of the periodical within the volume
2
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
80
UT code for WoS article
000511398100002
EID of the result in the Scopus database
2-s2.0-85078871083