A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00473055" target="_blank" >RIV/68378050:_____/16:00473055 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.18632/oncotarget.7836" target="_blank" >http://dx.doi.org/10.18632/oncotarget.7836</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.18632/oncotarget.7836" target="_blank" >10.18632/oncotarget.7836</a>
Alternative languages
Result language
angličtina
Original language name
A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis
Original language description
A Disintegrin And Metalloprotease (ADAM) 10 exerts essential roles during organ development and tissue integrity in different organs, mainly through activation of the Notch pathway. However, only little is known about its implication in liver tissue physiology. Here we show that in contrast to its role in other tissues, ADAM10 is dispensable for the Notch2-dependent biliary tree formation. However, we demonstrate that expression of bile acid transporters is dependent on ADAM10. Consequently, mice deficient for Adam10 in hepatocytes, cholangiocytes and liver progenitor cells develop spontaneous hepatocyte necrosis and concomitant liver fibrosis. We furthermore observed a strongly augmented ductular reaction in 15-week old ADAM10(Delta hep/Delta ch) mice and demonstrate that c-Met dependent liver progenitor cell activation is enhanced. Additionally, liver progenitor cells are primed to hepatocyte differentiation in the absence of ADAM10. These findings show that ADAM10 is a novel central node controlling liver tissue homeostasis. Highlights: Loss of ADAM10 in murine liver results in hepatocyte necrosis and concomitant liver fibrosis. ADAM10 directly regulates expression of bile acid transporters but is dispensable for Notch2-dependent formation of the biliary system.Activation of liver progenitor cells is enhanced through increased c-Met signalling, in the absence of ADAM10. Differentiation of liver progenitor cells to hepatocytes is augmented in the absence of ADAM10.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EB - Genetics and molecular biology
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
OncoTarget
ISSN
1949-2553
e-ISSN
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Volume of the periodical
7
Issue of the periodical within the volume
14
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
17431-17441
UT code for WoS article
000375699000014
EID of the result in the Scopus database
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