Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis.
OBJECTIVE
Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared.


METHODS
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.


CONCLUSIONS
PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis.
Huang
Xiao X
XX
A W Morrow Gastroenterology and Liver Centre at Royal Prince Alfred Hospital, NSW, Australia.
McCaughan
Geoffrey W
GW
Shackel
Nicholas A
NA
Gorrell
Mark D
MD
D000293:Adolescent; D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000032:analysis; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000821:virology; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000032:analysis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051076:Proto-Oncogene Proteins c-fyn / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051193:Toll-Like Receptors / Q000032:analysis; D014157:Transcription Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
C111180:BCL9 protein, human; D019485:Bone Morphogenetic Proteins; C066855:HGF protein, human; D009363:Neoplasm Proteins; C000608036:PGF protein, human; C490587:PIM2 protein, human; D011257:Pregnancy Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D014157:Transcription Factors; D000072483:Placenta Growth Factor; D017228:Hepatocyte Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; D017346:Protein Serine-Threonine Kinases