title: Extrahepatic cholangiocyte cilia are abnormal in biliary atresia.
abstract: OBJECTIVE
  Biliary atresia (BA) is a rapidly progressive form of biliary fibrosis affecting neonates. We previously reported that primary cilia on the intrahepatic cholangiocytes of patients with both syndromic and nonsyndromic BA were structurally abnormal. Our objective was to determine whether extrahepatic cholangiocytes in human biliary atresia, intrahepatic and extrahepatic cholangiocytes of rhesus rotavirus (RRV)-infected neonatal mice, and RRV-infected primary neonatal extrahepatic cholangiocytes also demonstrate ciliary abnormalities.
  
  
  METHODS
  The livers of neonatal BALB/c mice injected with RRV that developed jaundice, human extrahepatic bile duct samples obtained at time of hepatoportoenterostomy, and RRV-infected primary neonatal cholangiocytes were stained with antibodies against acetylated α tubulin to identify primary cilia.
  
  
  RESULTS
  Extrahepatic cholangiocytes from RRV-treated mice demonstrated minimal loss of primary cilia at day 3 but almost complete loss at day 8 and partial loss at day 12. No changes were seen in mouse intrahepatic bile ducts at any of the time points. In the human BA samples, primary cilia were almost completely absent from extrahepatic duct cholangiocytes. There were, however, abundant cilia in the peribiliary glands adjacent to extrahepatic ducts in the BA sample. Cilia in RRV-infected primary neonatal cholangiocytes were significantly decreased compared with controls.
  
  
  CONCLUSIONS
  Primary cilia are selectively lost from neonatal extrahepatic but not intrahepatic cholangiocytes after RRV infection in BALB/c mice. The cilia are also decreased in RRV-infected primary cholangiocytes and the extrahepatic ducts from human patients with BA. This suggests that ciliary abnormalities are part of the pathophysiology of BA.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Karjoo
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hand
authors.forename: Lorena
authors.initials: L
authors.lastname: Loarca
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Russo
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Friedman
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Wells
mesh_terms: D000107:Acetylation; D000818:Animals; D000831:Animals, Newborn; D017734:Bile Ducts, Extrahepatic / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology / Q000821:virology; D001656:Biliary Atresia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002923:Cilia / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000209:etiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D011499:Protein Processing, Post-Translational; D012401:Rotavirus / Q000254:growth & development; D012400:Rotavirus Infections / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014404:Tubulin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014404:Tubulin