Melatonin receptor 1A, but not 1B, knockout decreases biliary damage and liver fibrosis during cholestatic liver injury.

ABSTRACT:

Background and aims

Melatonin reduces biliary damage and liver fibrosis in cholestatic models by interaction with melatonin receptors 1A (MT1) and 1B (MT2). MT1 and MT2 can form heterodimers and homodimers, but MT1 and MT2 can heterodimerize with the orphan receptor G protein-coupled receptor 50 (GPR50). MT1/GPR50 dimerization blocks melatonin binding, but MT2/GPR50 dimerization does not affect melatonin binding. GPR50 can dimerize with TGFβ receptor type I (TGFβRI) to activate this receptor. We aimed to determine the differential roles of MT1 and MT2 during cholestasis.

Approach and results

Wild-type (WT), MT1 knockout (KO), MT2KO, and MT1/MT2 double KO (DKO) mice underwent sham or bile duct ligation (BDL); these mice were also treated with melatonin. BDL WT and multidrug r

SUBMITTER: Wu N 

PROVIDER: S-EPMC8930565 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature