title: Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis.
abstract: Tight junctions (TJ) of biliary epithelial cells (BEC) and hepatocytes prevent bile regurgitation from the biliary tract. Alterations in these TJs may participate in chronic cholestatic liver diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). We examined the localization of 2 TJ proteins, ZO-1 and 7H6, in these diseases. Frozen sections from livers of PBC, PSC, extrahepatic cholestasis (Ex-C), and hepatitis C-associated cirrhosis (LC-C), as well as histologically normal livers, were processed for double-fluorescence immunohistochemistry. In controls and cirrhosis, 7H6 and ZO-1 colocalized surrounding the luminal space of the bile ducts and outlined the bile canalicular spaces between hepatocytes. In untreated PBC, immunostaining for ZO-1 in BEC of bile ducts 40 to 80 microm in diameter was preserved, but that for 7H6 was diminished to absent. In PBC treated with ursodeoxycholic acid (UDCA), immunostaining for 7H6 was well preserved. In PSC as well as in Ex-C, immunostaining for both 7H6 and ZO-1 was well preserved in bile ducts. In hepatocytes, ZO-1 showed preserved immunoreactivity, but immunostaining for 7H6 frequently disappeared. The percentage of bile ducts with immunostaining for 7H6 in all bile ducts with immunostaining for ZO-1 was significantly reduced in PBC compared with that in control, LC-C, Ex-C, and PSC (all P <.0001). Substantial alteration in the TJ protein occurs predominantly in bile ducts in PBC and in hepatocytes in PSC, suggesting increased paracellular permeability along different paracellular routes for bile regurgitation in these chronic cholestatic liver diseases.
authors.affiliation: Third Department of Medicine, Fukuoka University School of Medicine, Fukuoka, Japan. sakisaka@fukuoka-u.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Sakisaka
authors.forename: T
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: E
authors.initials: E
authors.lastname: Taniguchi
authors.forename: S
authors.initials: S
authors.lastname: Hanada
authors.forename: K
authors.initials: K
authors.lastname: Sasatomi
authors.forename: H
authors.initials: H
authors.lastname: Koga
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: R
authors.initials: R
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Sata
authors.forename: N
authors.initials: N
authors.lastname: Sawada
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: S
authors.initials: S
authors.lastname: Todo
authors.forename: T
authors.initials: T
authors.lastname: Kurohiji
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001652:Bile Ducts / Q000378:metabolism; D015209:Cholangitis, Sclerosing / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism; D013194:Staining and Labeling; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure*; D014018:Tissue Distribution; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C089734:antigen 7H6