The receptor TGR5 protects the liver from bile acid overload during liver regeneration in mice

• DOI: 10.1002/hep.26463
• Publication Date: 2013-05-17T13:36:01Z
• Authors: Noémie Péan; Isabelle Doignon; Isabelle Garcin; Aurore Besnard; Boris Julien; Bingkaï Liu; Sophie Branchereau; Anne Spraul; Catherine Guettier; Lydie Humbert; Kristina Schoonjans; Dominique Rainteau; Thierry Tordjmann
• Keywords: Liver Regeneration; Farnesoid X receptor; Lithocholic acid; Ursodeoxycholic acid; Deoxycholic acid

Many regulatory pathways are involved in liver regeneration after partial hepatectomy (PH) to initiate growth, protect cells, and sustain functions of the remnant liver. Bile acids (BAs), whose levels rise blood early PH, stimulate both hepatocyte proliferation protection, part through their binding nuclear farnesoid X receptor (FXR). However, effect BA receptor, TGR5 (G-protein-coupled 1) PH remains be studied. Liver histology, proliferation, concentrations (plasma, bile, liver, urine, feces), bile flow composition, cytokine production were studied wild-type (WT) KO (knockout) mice before PH. composition feces) was more hydrophobic than WT mice. After severe necrosis, prolonged cholestasis, exacerbated inflammatory response, delayed observed Although adaptive response post-PH overload similar mice, kidney biliary responses strongly impaired Cholestyramine treatment, as well Kupffer cell depletion, significantly improved phenotype. duct ligation or upon a cholic acid-enriched diet, exhibited injury elimination urine.TGR5 is crucial for protection against primarily control hydrophobicity secretion. In absence TGR5, intrahepatic stasis abnormally excessive inflammation, association with adaptation deficient urinary efflux, lead overload-induced regeneration.