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The secretin receptor antagonist (SCT 5‐27) reduces biliary hyperplasia and liver fibrosis in an animal model of primary sclerosing cholangitis

Secretin (SCT) is trophic and profibrotic hormone produced by the S cells of the duodenum as well as cholangiocytes. The SCT/secretin receptor (SR) axis stimulates biliary proliferation in normal and cholestatic mice following bile duct ligation (BDL). We have shown that SCT down‐regulates the expression of the miRNAs, miR‐125b and let‐7a, which target the expression of VEGF‐A and NGF, respectively, that are proliferative factors that stimulate biliary proliferation during cholestasis. The AIM of our study was to evaluate the effect of inhibition of the SCT/SR axis with Sec 5‐27 on biliary proliferation and liver fibrosis in the Mdr2−/− mouse model of primary sclerosing cholangitis (PSC). PSC is a disease characterized by inflammation of cholangiocytes that leads to scar formation and duct obstruction with subsequent cirrhosis and liver failure.