ADAM10/17-dependent release of soluble c-Met correlates with hepatocellular damage
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
23746173
PII: file/5682/FB2013A0009.pdf
Knihovny.cz E-zdroje
- MeSH
- alanintransaminasa krev MeSH
- aspartátaminotransferasy krev MeSH
- bilirubin metabolismus MeSH
- biologické markery metabolismus MeSH
- buňky Hep G2 MeSH
- hepatocyty metabolismus patologie MeSH
- jaterní hvězdicovité buňky metabolismus patologie MeSH
- játra metabolismus patologie MeSH
- lidé MeSH
- membránové proteiny metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nemoci jater krev metabolismus patologie MeSH
- protein ADAM10 MeSH
- protein ADAM17 MeSH
- proteiny ADAM metabolismus MeSH
- protoonkogenní proteiny c-met krev metabolismus MeSH
- rozpustnost MeSH
- sekretasy metabolismus MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ADAM10 protein, human MeSH Prohlížeč
- ADAM17 protein, human MeSH Prohlížeč
- Adam17 protein, mouse MeSH Prohlížeč
- alanintransaminasa MeSH
- aspartátaminotransferasy MeSH
- bilirubin MeSH
- biologické markery MeSH
- membránové proteiny MeSH
- messenger RNA MeSH
- protein ADAM10 MeSH
- protein ADAM17 MeSH
- proteiny ADAM MeSH
- protoonkogenní proteiny c-met MeSH
- sekretasy MeSH
The signalling pathway elicited by hepatocyte growth factor (HGF) and its receptor c-Met is indispensable for liver development and regeneration. It has been described that c-Met is released from the cell surface by a disintegrin and metalloprotease 10 (ADAM10) resulting in a soluble c-Met form known as sMet. Using the human hepatocellular HepG2 and hepatic stellate cell LX2 lines we show that sMet is released from the cell surface of liver cells by both ADAM17 and ADAM10, with ADAM17 appearing to be the major proteinase. Moreover, using a mouse model of 3,5-diethoxycarbonyl- 1,4-dihydroxycollidine (DDC)-induced hepatobiliary obstruction we show that serum levels of sMet correlate well with the liver damage state and consecutive regeneration as well as with established markers of liver damage such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin. However, sMet exhibited remarkably better correlation with liver damage and inflammation than did serum tumour necrosis factor α (TNF-α), whose shedding is also mediated by ADAM proteolytic activity. Our results indicate that the proteolytic activity of ADAM10/17 is essential for regulating HGF/c-Met signalling during acute liver damage and following regeneration and that the differential serum levels of sMet together with expression of c-Met/HGF might be a useful indicator not only for damage, but also for ongoing liver regeneration.
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Liver protective effect of ursodeoxycholic acid includes regulation of ADAM17 activity