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Anim Cells Syst (Seoul). 2019 Jun 9;23(3):170-175. doi: 10.1080/19768354.2019.1595141. eCollection 2019 Jun.

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

Cho TJ1,2, Kim HJ2, Cho J1,2.

Author information

1
Labratory of Developmental Biology and Stem Cell Differentiation/Transplantation, Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University South Korea, Seoul, South Korea.
2
Dental Research Institute, Seoul National University, Seoul, South Korea.

Abstract

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.

KEYWORDS:

Endothelin-converting enzyme-1; endothelin receptor; endothelin-1; hepatic fibrogenesis

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