*Present address: Dermatology Department, The University of Sydney, NSW, Australia.
Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis
Article first published online: 13 AUG 2007
Volume 27, Issue 7, pages 960–968, September 2007
How to Cite
Huang, X. X., McCaughan, G. W., Shackel, N. A. and Gorrell, M. D. (2007), Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis. Liver International, 27: 960–968. doi: 10.1111/j.1478-3231.2007.01542.x
- Issue published online: 13 AUG 2007
- Article first published online: 13 AUG 2007
- Received 23 November 2006accepted 3 May 2007
- hepatitis C virus;
- hepatocellular carcinoma;
- placental growth factor;
- vascular endothelial growth factor
Background/Aims: Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared.
Method: Proliferation pathway genes, immune response genes and oncogenes were analysed by a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining.
Results: Real-time RT-PCR showed up-regulation of genes in HCV cirrhosis including the proliferation-associated genes bone morphogenetic protein 3 (BMP3), placental growth factor 3 (PGF3), vascular endothelial growth factor receptor 1 (VEGFR1) and soluble VEGFR1, the oncogene FYN, and the immune response-associated genes toll-like receptor 9 (TLR9) and natural killer cell transcript 4 (NK4). Expressions of TLR2 and the oncogenes B-cell CLL/lymphoma 9 (BCL9) and PIM2 were decreased in HCV cirrhosis. In addition, PIM2 and TLR2 were increased in HCV cirrhosis with HCC compared with HCV cirrhosis. The ligand/receptor pair PGF and VEGFR1 was intensely expressed by the portal tract vascular endothelium. VEGFR1 was expressed in reactive biliary epithelial structures in fibrotic septum and in some stellate cells and macrophages.
Conclusion: PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis.