title: Animal models of biliary tract injury.
abstract: OBJECTIVE
  Cholestatic liver diseases with bile duct injury and biliary fibrosis account for a significant percentage of patients with end-stage liver disease and undergoing liver transplantation. A number of different animal models have been established and have added substantially to our understanding of the molecular mechanisms underlying this group of chronic liver diseases. In the present review, we discuss recent findings and new insight derived from different animal models of biliary tract injury and fibrosis.
  
  
  RESULTS
  Cholangiocytes do not undergo epithelial to mesenchymal transition and do not contribute to the pool of biliary fibroblasts involved in extracellular matrix deposition. Rather cholangiocytes can acquire a reactive phenotype activating fibrogenesis through secretion of proinflammatory and profibrogenic mediators. Bile acid homeostasis is controlled by a gut-liver axis playing a crucial role in the adaptive response to bile duct injury and cholestasis. The nuclear factor-kappa B and hedgehog signaling pathways play a critical role in cholestatic liver injury and the emergence of liver cancer. Nuclear receptors are key mediators of adaptive response mechanisms in cholestasis and potential therapeutical targets.
  
  
  CONCLUSIONS
  Recent progress and mechanistic insights from mouse models have added to our understanding of the molecular mechanisms underlying cholestatic liver and biliary tract injury and pointed to new therapeutic options.
authors.affiliation: Institute of Pharmacology, Center for Physiology and Pharmacology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Österreicher
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
mesh_terms: D000818:Animals; D001659:Biliary Tract / Q000293:injuries / Q000473:pathology*; D002779:Cholestasis / Q000473:pathology*; D004195:Disease Models, Animal; D005355:Fibrosis; D053823:Hedgehog Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; C501916:Ppp1r13l protein, mouse; D012097:Repressor Proteins