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Lack of Fas antagonism by Met in human fatty liver disease.
- Source :
- Nature Medicine; Sep2007, Vol. 13 Issue 9, p1078-1085, 8p, 1 Black and White Photograph, 5 Graphs
- Publication Year :
- 2007
-
Abstract
- Hepatocytes in fatty livers are hypersensitive to apoptosis and undergo escalated apoptotic activity via death receptor–mediated pathways, particularly that of Fas-FasL, causing hepatic injury that can eventually proceed to cirrhosis and end-stage liver disease. Here we report that the hepatocyte growth factor receptor, Met, plays an important part in preventing Fas-mediated apoptosis of hepatocytes by sequestering Fas. We also show that Fas antagonism by Met is abrogated in human fatty liver disease (FLD). Through structure-function studies, we found that a YLGA amino-acid motif located near the extracellular N terminus of the Met α-subunit is necessary and sufficient to specifically bind the extracellular portion of Fas and to act as a potent FasL antagonist and inhibitor of Fas trimerization. Using mouse models of FLD, we show that synthetic YLGA peptide tempers hepatocyte apoptosis and liver damage and therefore has therapeutic potential. [ABSTRACT FROM AUTHOR]
- Subjects :
- LIVER diseases
FATTY liver
LIVER cells
PEPTIDES
APOPTOSIS
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 13
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 26506355
- Full Text :
- https://doi.org/10.1038/nm1625