Knockout of the Tachykinin Receptor 1 in the Mdr2^-/- (Abcb4^-/-) Mouse Model of Primary Sclerosing Cholangitis Reduces Biliary Damage and Liver Fibrosis.

ABSTRACT: Activation of the substance P (SP)/neurokinin 1 receptor (NK1R) axis triggers biliary damage/senescence and liver fibrosis in bile duct ligated and Mdr2^-/- (alias Abcb4^-/-) mice through enhanced transforming growth factor-β1 (TGF-β1) biliary secretion. Recent evidence indicates a role for miR-31 (MIR31) in TGF-β1-induced liver fibrosis. We aimed to define the role of the SP/NK1R/TGF-β1/miR-31 axis in regulating biliary proliferation and liver fibrosis during cholestasis. Thus, we generated a novel model with double knockout of Mdr2^-/- and NK1R^-/ (alias Tacr1^-/-) to further address the role of the SP/NK1R axis during chronic cholestasis. In vivo studies were performed in the following 12-week-old male mice: (i) NK1R^-/-; (ii)

SUBMITTER: Ceci L 

PROVIDER: S-EPMC7592721 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature