Therapeutic effects of FXR and TGR5 activation in the Mdr2 (Abcb4)-/-
Results of a study presented today at the International Liver CongressTM 2010 demonstrate that a dual FXR and TGR5 agonist decreases liver damage and modulates hepatic inflammation and fibrosis in a mouse model of primary sclerosing chlolangitis. In contrast, selective FXR or TGR5 agonists have no beneficial effect.
FXR and TGR5 agonists are responsible for regulating bile acids, glucose, lipids and inflammation.
Primary sclerosing cholangitis (PSC) is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts. Inflammation impedes the flow of bile to the gut, and can ultimately lead to liver cirrhosis, liver failure and liver cancer. The underlying cause of inflammation is thought to be autoimmunity. The definitive treatment is liver transplantation.
Liver cells effectively serve as immune checkpoint regulating anti-cancer immunity