Expression of connective tissue growth factor in the human liver with idiopathic portal hypertension.
Idiopathic portal hypertension (IPH) is a disorder of unknown etiology, clinically associated with portal hypertension in the absence of cirrhosis. This study was designed to delineate the characteristics of IPH RNA expression in liver specimens from patients with IPH. Liver specimens from patients with IPH and patients without liver diseases underwent cDNA expression analysis and in situ hybridization studies. Connective tissue growth factor (CTGF) levels in serum were examined in 76 patients with IPH, 84 patients with hepatitis C virus infection (including those with cirrhosis), and 38 healthy volunteers. Among 588 genes sorted on macroarray, seven up-regulated genes, including CTGF, were detected. In situ hybridization studies showed that positive reactions for CTGF mRNA were most intense in the epithelial cells of proliferating bile ducts within portal tracts in patients with IPH. In the liver parenchyma, there was no appreciable staining of hepatocytes, sinusoidal endothelial cells, or hepatic stellate cells (HSCs), and there were few positive signals for CTGF mRNA in normal liver. The serum CTGF level in patients with IPH was significantly higher than the value in healthy volunteers. Six (8%) of the 76 patients with IPH had serum CTGF levels greater than 80 ng/mL, far exceeding the level of any patient with cirrhosis. In conclusion, overexpression of CTGF is one of the most important features of IPH.
Morikawa
Hiroyasu
H
Department of Hepatology, Osaka City University Graduate School of Medicine, Asahimachi, Osaka, Japan.
Tamori
Akihiro
A
Nishiguchi
Shuhei
S
Enomoto
Masaru
M
Habu
Daiki
D
Kawada
Norifumi
N
Shiomi
Susumu
S
D055513:Connective Tissue Growth Factor; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006975:Hypertension, Portal / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
C526317:CCN2 protein, human; D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor