Increased susceptibility to severe chronic liver damage in CXCR4 conditional knock-out mice.
Dig Dis Sci
; 57(11): 2892-900, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-22674400
ABSTRACT
BACKGROUND:
The chemokine SDF-1 and its receptor CXCR4 are essential for the proper functioning of multiple organs. In the liver, cholangiocytes and hepatic progenitor cells (HPCs) are the main cells that produce SDF-1, and SDF-1 is thought to be essential for HPC-stimulated liver regeneration.AIMS:
In this study, CXCR4 conditionally targeted mice were used to analyze the role of SDF-1 in chronically damaged liver.METHODS:
Chronic liver damage was induced in MxCre CXCR4(f/null) mice and the control MxCre CXCR4(f/wt) mice by CCl(4). Serum markers were analyzed to assess liver function and damage, the number of cytokeratin-positive cells as a measure of HPCs, and the extent of liver fibrosis. Additional parameters relating to liver damage, such as markers of HPCs, liver function, MMPs, and TIMPs were measured by real-time PCR.RESULTS:
Serum ALT was significantly higher in MxCre CXCR4(f/null) mice than MxCre CXCR4(f/wt) mice. The number of cytokeratin-positive cells and the area of fibrosis were also increased in the MxCre CXCR4(f/null) mice. The expression of mRNAs for several markers related to hepatic damage and regeneration was also increased in the liver of MxCre CXCR4(f/null) mice, including primitive HPC marker prominin-1, MMP9, TNF-α, and α-SMA.CONCLUSIONS:
MxCre CXCR4(f/null) mice were susceptible to severe chronic liver damage, suggesting that SDF-1-CXCR4 signals are important for liver regeneration and preventing the progression of liver disease. Modulation of SDF-1 may therefore be a promising treatment strategy for patients with chronic liver disease.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores CXCR4
/
Quimiocina CXCL12
/
Hepatopatias
Limite:
Animals
Idioma:
En
Revista:
Dig Dis Sci
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Japão