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GGPPSdeficiency aggravates CCl4-induced liver injury by inducing hepatocyte apoptosis
- Source :
- FEBS Letters. 589:1119-1126
- Publication Year :
- 2015
- Publisher :
- Wiley, 2015.
-
Abstract
- GGPPS catalyses the expression of GGPP, a key protein in the mevalonate metabolic pathway. HMG-CoA reductase inhibitor statins can induce liver injury by inhibiting GGPP. However, the function of GGPPS in liver injury has not yet been revealed. In this study, we found that GGPPS increased in liver injury and that GGPPS deletion augmented liver injury and fibrosis. GGPPS inhibition induced hepatocyte apoptosis, inflammation and TGF-β1 secretion, which activated hepatic stellate cells. Our findings imply that GGPPS deletion induces hepatocyte apoptosis, which makes the liver vulnerable to hepatotoxicity.
- Subjects :
- Liver Cirrhosis
MAPK/ERK pathway
Liver fibrosis
Biophysics
Inflammation
Liver injury
Biochemistry
Transforming Growth Factor beta1
Hepatocyte apoptosis
Mice
Polyisoprenyl Phosphates
Structural Biology
Fibrosis
Genetics
medicine
Animals
Farnesyltranstransferase
Molecular Biology
Glyceraldehyde 3-phosphate dehydrogenase
Mice, Knockout
biology
Carbon Tetrachloride Poisoning
Cell Biology
medicine.disease
Geranylgeranyl diphosphate synthase
CTGF
Liver
HMG-CoA reductase
Hepatocytes
biology.protein
Cancer research
Hepatic stellate cell
medicine.symptom
Gene Deletion
Subjects
Details
- ISSN :
- 00145793
- Volume :
- 589
- Database :
- OpenAIRE
- Journal :
- FEBS Letters
- Accession number :
- edsair.doi.dedup.....7b884d71118e6df2d5d6ed17446b563f
- Full Text :
- https://doi.org/10.1016/j.febslet.2015.03.015