Localization of the therapeutic targets for endothelin receptor antagonists and sodium-glucose co-transporter 2 inhibitors in the chronic liver disease, primary sclerosing cholangitis.

ABSTRACT:

Introduction

Primary sclerosing cholangitis (PSC) is a chronic liver disease of unknown cause contributing to cirrhosis and cancer but has no cure. PSC is characterized by inflammation within ductal fibrosis, progressive bile duct narrowing and loss, with damage to cholangiocytes (epithelial cells affecting bile production) and liver repair. ET-1, produced by cholangiocytes, contributes to fibrosis, vasoconstriction, and inflammation via ET_A receptors. In patients, ET-1 and ET_A gene expression are elevated and ET_A antagonists reduce disease progression in PSC animal models. Ongoing clinical trials of portal hypertension in liver disease are testing the efficacy of a new treatment strategy combining ET_A-selective antagonist zibotentan with

SUBMITTER: Kuc RE 

PROVIDER: S-EPMC12516093 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature