Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating plasma endothelin-1 (ET-1) is elevated in liver cirrhosis, in a disease-stage-dependent manner. However, ET-1 exerts its effects mainly via paracrine and autocrine pathways. Therefore, the aim of the present study was to analyze the hepatic endothelin (ET) system in liver cirrhosis resulting from bile duct obstruction (BDO). Wistar rats were subjected for 6 weeks to either sham operation (control) or BDO. Thereafter, hepatic ET-1 concentrations were elevated 7.2-fold in BDO compared to control (p <0.001), whereas big ET-1 was unchanged. The density of both ET receptor subtypes was upregulated in BDO (ETA: 7.4-fold and ETB: 4.9-fold vs control, p < 0.001, respectively). The affinity of both receptor subtypes was significantly reduced in BDO. In conclusion, our data demonstrated for the first time that the hepatic ET system in liver cirrhosis is characterized by a simultaneous upregulation of both ET-1 tissue concentration as well as the density of hepatic ETA- and ETB-receptors, suggesting a synergistic activation of the hepatic ET system in rats with BDO. The increased ET-1 tissue concentration is not a result of an altered big ET-1 synthesis in biliary liver fibrosis, suggesting an increased activity of endothelin-converting enzyme (ECE) in liver cirrhosis.
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PMID:Activation of the hepatic endothelin-system in rats with biliary liver fibrosis. 1107 96

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.
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PMID:Expression of the hepatic endothelin system in human cirrhotic livers. 1537 55

The progression of rat liver fibrosis induced by intraperitoneal administration of thioacetamide (TAA) was evaluated by immunocytochemistry using anti-alpha-smooth muscle actin (alpha-SMA), antiendothelin-converting enzyme (ECE)-1, and anti-monocyte chemotactic protein (MCP)-1 antibodies. The fibrous septal spaces gradually increased after administration of TAA, and pseudolobules were established in the 7-week TAA-treated groups. Immunoreactivities against alpha-SMA were not detected in hepatic stellate cells (HSCs) of the control group without TAA treatment, although they were observed in the HSCs around the fibrous septal spaces in all TAA-treated groups, indicating that activation of HSCs occurs during the establishment of pseudolobules. Immunoreactivities against ECE-1 and MCP-1 were seen in such HSCs of the TAA-treated groups, but few or no immunoreactivities were detected in the HSCs of the control group. The most significant increase in the ECE-1 immunoreactivities was detected in the 1-week TAA-treated group, whereas that in MCP-1 was observed in the 7-week TAA-treated group. The present immunocytochemistry indicated a difference in the accelerated expression period between immunoreactivities against ECE-1 and MCP-1 in the HSCs during the progression of TAA-induced liver fibrosis, suggesting that ECE-1 is involved in the early phase of liver fibrosis and that MCP-1 plays a role during the later phase.
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PMID:Increased immunoreactivities against endothelin-converting enzyme-1 and monocyte chemotactic protein-1 in hepatic stellate cells of rat fibrous liver induced by thioacetamide. 1617 Apr 64