title: Bile canalicular abnormalities in the early phase of a mouse model of sclerosing cholangitis.
abstract: BACKGROUND
  The bile canaliculus is the smallest and first biliary channel and is formed by two or three adjacent hepatocytes. Previous studies of chronic cholangiopathies such as primary sclerosing cholangitis have focused on the bile ductules. However, little is known about the pathological alterations in bile canaliculi in the early phase of cholangiopathies.
  
  
  OBJECTIVE
  To characterize the bile canalicular morphology in the early phase of sclerosing cholangitis we used 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced mouse model of sclerosing cholangitis.
  
  
  METHODS
  Mice were fed a diet with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (0.1%). Serum biochemical, histological, immunohistochemical, and electron microscopic analyses were performed 1, 2, 4, and 7 days after feeding.
  
  
  RESULTS
  All experimental groups showed significantly increased serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels. From day 1, bile canalicular abnormalities such as dilatation and meandering and loss of microvilli were observed. After bile canalicular abnormalities had appeared, substantial infiltration of inflammatory cells was observed amongst the necrotic cells and periductal region. After these inflammatory changes, cholangiocytes proliferated in the portal area and formed ductular reactions. Finally, periductal fibrosis appeared.
  
  
  CONCLUSIONS
  This study provides novel evidence of the occurrence of bile canalicular abnormalities during the early phase of sclerosing cholangitis.
authors.affiliation: Department of Forensic Medicine and Molecular Pathology, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Miyao
authors.forename: Munetaka
authors.initials: M
authors.lastname: Ozeki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Abiru
authors.forename: Sho
authors.initials: S
authors.lastname: Manabe
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kotani
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.forename: Keiji
authors.initials: K
authors.lastname: Tamaki
mesh_terms: D000818:Animals; D001648:Bile Canaliculi / Q000473:pathology* / Q000648:ultrastructure; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D015209:Cholangitis, Sclerosing / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D008099:Liver / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011725:Pyridines
chemical_list: C530773:3,5-diethoxycarbonyl-1,4-dihydrocollidine; D011725:Pyridines