title: Wnt signaling regulates hepatobiliary repair following cholestatic liver injury in mice.
abstract: Hepatic repair is directed chiefly by the proliferation of resident mature epithelial cells. Furthermore, if predominant injury is to cholangiocytes, the hepatocytes can transdifferentiate to cholangiocytes to assist in the repair and vice versa, as shown by various fate-tracing studies. However, the molecular bases of reprogramming remain elusive. Using two models of biliary injury where repair occurs through cholangiocyte proliferation and hepatocyte transdifferentiation to cholangiocytes, we identify an important role of Wnt signaling. First we identify up-regulation of specific Wnt proteins in the cholangiocytes. Next, using conditional knockouts of Wntless and Wnt coreceptors low-density lipoprotein-related protein 5/6, transgenic mice expressing stable β-catenin, and in vitro studies, we show a role of Wnt signaling through β-catenin in hepatocyte to biliary transdifferentiation. Last, we show that specific Wnts regulate cholangiocyte proliferation, but in a β-catenin-independent manner.
  
  
  
  Wnt signaling regulates hepatobiliary repair after cholestatic injury in both β-catenin-dependent and -independent manners. (Hepatology 2016;64:1652-1666).
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.|Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Okabe
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Sylakowski
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Mladen
authors.initials: M
authors.lastname: Yovchev
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyagawa
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Nagarajan
authors.affiliation: Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Maria
authors.initials: M
authors.lastname: Chikina
authors.affiliation: Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH.
authors.forename: Michael
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Michael
authors.initials: M
authors.lastname: Oertel
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.|Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Satdarshan P
authors.initials: SP
authors.lastname: Monga
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA. knnst5@pitt.edu.
authors.forename: Kari Nichole
authors.initials: KN
authors.lastname: Nejak-Bowen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D054338:Cell Transdifferentiation; D002780:Cholestasis, Intrahepatic; D022781:Hepatocytes; D006801:Humans; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin