Expression of the hepatic endothelin system in human cirrhotic livers.
It is considered that endothelin-1 participates in the development of liver cirrhosis and it has been recognized that every component of the endothelin system is upregulated in cirrhotic livers. However, the expression pattern of this system, including interaction between its components, is not fully understood in human livers. In this study, the expression pattern of the endothelin system was examined. Immunohistochemical analysis for endothelin-1, endothelin receptors and endothelin-converting enzyme was performed in 16 cirrhotic and 17 normal human liver tissues. Peptides, proteins, and RNAs extracted from the livers were also investigated using quantitative assays for the components of the hepatic endothelin system. Hepatic endothelin-1 levels were significantly higher in cirrhotic livers (0.084 +/- 0.052 pg/mg wet liver) than in normal livers (0.041 +/- 0.032 pg/mg; p < 0.01), and were closely related to the severity of liver fibrosis and portal hypertension. Immunoreactivity for endothelin-1, endothelin receptors, and endothelin-converting enzyme was detected mainly in fibrous areas and in the hepatic vasculature, and was enhanced in cirrhosis. Although there was a negative correlation between the expression of receptor mRNA and the hepatic endothelin-1 level, the amounts of the mRNAs were greater in cirrhotic livers than in normal livers. However, expression of endothelin-converting enzyme in cirrhotic livers was increased at the protein level but was relatively reduced at the mRNA level. These findings suggest that the hepatic endothelin system is activated in human cirrhotic livers in association with worsening of the disease, but that the regulation of the components of this system in this disorder is complex.
Ikura
Yoshihiro
Y
Department of Pathology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan. ikura@med.osaka-cu.ac.jp
Ohsawa
Masahiko
M
Naruko
Takahiko
T
Muraguchi
Takashi
T
Hirayama
Michihiko
M
Suekane
Takehisa
T
Fukushima
Hiroko
H
Sugama
Yoshimi
Y
Shirai
Nobuyuki
N
Kayo
Soichiro
S
Yoshimi
Noriko
N
Ehara
Shoichi
S
Tanzawa
Kazuhiko
K
Ueda
Makiko
M
D000368:Aged; D016282:Aspartic Acid Endopeptidases / Q000032:analysis*; D015153:Blotting, Western / Q000379:methods; D019332:Endothelin-1 / Q000032:analysis*; D000072396:Endothelin-Converting Enzymes; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D044022:Receptor, Endothelin A / Q000032:analysis; D044023:Receptor, Endothelin B / Q000032:analysis; D017466:Receptors, Endothelin / Q000032:analysis*; D012720:Severity of Illness Index
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes