Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis

Endothelin-1 (ET-1) induces contraction, proliferation, and collagen synthesis of activated hepatic stellate cells and is a potent mediator of portal hypertension. Endothelin-converting enzyme-1 (ECE-1) generates ET-1 from the inactive precursor big-endothelin-1. The cellular distribution and activi...

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Main Authors: Tae-Jun Cho, Hyo-Jung Kim, Jaejin Cho
Format: Article
Language:English
Published: Taylor & Francis Group 2019-05-01
Series:Animal Cells and Systems
Subjects:
Online Access:http://dx.doi.org/10.1080/19768354.2019.1595141
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author Tae-Jun Cho
Hyo-Jung Kim
Jaejin Cho
author_facet Tae-Jun Cho
Hyo-Jung Kim
Jaejin Cho
author_sort Tae-Jun Cho
collection DOAJ
description Endothelin-1 (ET-1) induces contraction, proliferation, and collagen synthesis of activated hepatic stellate cells and is a potent mediator of portal hypertension. Endothelin-converting enzyme-1 (ECE-1) generates ET-1 from the inactive precursor big-endothelin-1. The cellular distribution and activity of ECE-1 in the liver is unknown. Hepatic fibrogenesis was induced in rats by CCl4 administration and secondary biliary cirrhosis after 6 weeks of complete bile duct occlusion (BDO). The tissue ET-1 and ET receptor protein levels were quantified, the ECE-1 isoform mRNAs were measured by RNase protection assay and ECE-1 activity was analyzed. ECE-1a and -b mRNA were upregulated in biliary cirrhosis and in CCl4-injured livers, whereas ECE-1c mRNA remained unchanged. ECE-1 activity was increased after BDO and peaked at 12 h after acute CCl4-intoxication. Tissue levels of ET-1, ETA- and ETB receptors were elevated 7-, 5-, and 4.6-fold in cirrhotic rats, respectively. ECE-1 activity increased following BDO and acute CCl4-intoxication. In conclusion, ECE-1a and -b RNAs are upregulated in fibrogenesis, indicating that these isoforms play a central role in ET-1 generation during fibrogenesis and portal hypertension.
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spelling doaj.art-d552e579b9404b6486b22e3fe673e89f2022-12-21T18:51:30ZengTaylor & Francis GroupAnimal Cells and Systems1976-83542151-24852019-05-0123317017510.1080/19768354.2019.15951411595141Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesisTae-Jun Cho0Hyo-Jung Kim1Jaejin Cho2School of Dentistry, Seoul National University South KoreaSeoul National UniversitySchool of Dentistry, Seoul National University South KoreaEndothelin-1 (ET-1) induces contraction, proliferation, and collagen synthesis of activated hepatic stellate cells and is a potent mediator of portal hypertension. Endothelin-converting enzyme-1 (ECE-1) generates ET-1 from the inactive precursor big-endothelin-1. The cellular distribution and activity of ECE-1 in the liver is unknown. Hepatic fibrogenesis was induced in rats by CCl4 administration and secondary biliary cirrhosis after 6 weeks of complete bile duct occlusion (BDO). The tissue ET-1 and ET receptor protein levels were quantified, the ECE-1 isoform mRNAs were measured by RNase protection assay and ECE-1 activity was analyzed. ECE-1a and -b mRNA were upregulated in biliary cirrhosis and in CCl4-injured livers, whereas ECE-1c mRNA remained unchanged. ECE-1 activity was increased after BDO and peaked at 12 h after acute CCl4-intoxication. Tissue levels of ET-1, ETA- and ETB receptors were elevated 7-, 5-, and 4.6-fold in cirrhotic rats, respectively. ECE-1 activity increased following BDO and acute CCl4-intoxication. In conclusion, ECE-1a and -b RNAs are upregulated in fibrogenesis, indicating that these isoforms play a central role in ET-1 generation during fibrogenesis and portal hypertension.http://dx.doi.org/10.1080/19768354.2019.1595141Endothelin-converting enzyme-1endothelin-1hepatic fibrogenesisendothelin receptor
spellingShingle Tae-Jun Cho
Hyo-Jung Kim
Jaejin Cho
Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis
Animal Cells and Systems
Endothelin-converting enzyme-1
endothelin-1
hepatic fibrogenesis
endothelin receptor
title Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis
title_full Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis
title_fullStr Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis
title_full_unstemmed Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis
title_short Endothelin-converting enzyme-1 expression in acute and chronic liver injury in fibrogenesis
title_sort endothelin converting enzyme 1 expression in acute and chronic liver injury in fibrogenesis
topic Endothelin-converting enzyme-1
endothelin-1
hepatic fibrogenesis
endothelin receptor
url http://dx.doi.org/10.1080/19768354.2019.1595141
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AT hyojungkim endothelinconvertingenzyme1expressioninacuteandchronicliverinjuryinfibrogenesis
AT jaejincho endothelinconvertingenzyme1expressioninacuteandchronicliverinjuryinfibrogenesis