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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection.

BACKGROUND/AIMS: The chemokine receptor CX3CR1 and its specific ligand fractalkine (CX3CL1) are known to modulate inflammatory and fibroproliferative diseases. Here we investigate the role of CX3CR1/fractalkine in HCV-induced liver fibrosis. METHODS: A genotype analysis of CX3CR1 variants was performed in 211 HCV-infected patients. Hepatic expression of CX3CR1 was studied in HCV-infected livers and isolated liver cell populations by RT-PCR and immunohistochemistry. The effects of fractalkine on mRNA expression of profibrogenic genes were determined in isolated hepatic stellate cells (HSC) and CX3CR1 genotypes were related to intrahepatic TIMP-1 mRNA levels. RESULTS: The intrahepatic mRNA expression of CX3CR1 correlates with the stage of HCV-induced liver fibrosis (P=0.03). The CX3CR1 coding variant V249I is associated with advanced liver fibrosis, independent of the T280M variant (P=0.009). CX3CR1 is present on primary HSC and fractalkine leads to a suppression of tissue inhibitor of metalloproteinase (TIMP)-1 mRNA in HSC (P=0.03). Furthermore, CX3CR1 genotypes are associated with TIMP-1 mRNA expression in HCV-infected liver (P=0.03). CONCLUSIONS: The results identify the fractalkine receptor CX3CR1 as susceptibility a gene for hepatic fibrosis in HCV infection. The modulation of TIMP-1 expression by fractalkine and CX3CR1 genotypes provides functional support for the observed genotype-phenotype association.[1]


  1. The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection. Wasmuth, H.E., Zaldivar, M.M., Berres, M.L., Werth, A., Scholten, D., Hillebrandt, S., Tacke, F., Schmitz, P., Dahl, E., Wiederholt, T., Hellerbrand, C., Berg, T., Weiskirchen, R., Trautwein, C., Lammert, F. J. Hepatol. (2008) [Pubmed]
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