title: Cholestasis in a rat model of graft-versus-host disease is accompanied by alteration of the expression and distribution of tight-junction-associated proteins.
abstract: Intrahepatic cholestasis has been recognized as one of the characteristic features of the hepatic manifestations in graft-versus-host disease (GVHD). Tight junctions (TJs) play crucial roles in bile formation and alterations of TJs in hepatocytes and/or biliary epithelial cells (BECs) that cause intrahepatic cholestasis. To assess the changes of TJs in hepatocytes and BECs in a rat model of GVHD, we examined the localization of TJ-associated proteins, 7H6 and zonula occludens (ZO)-1. GVHD was induced by injecting spleen cells of parental strain rats (Brown Norway) into non-irradiated (Brown Norway x Lewis) F1 hybrid rats. Untreated F1 hybrid rats served as controls. Double-labeled immunofluorescent staining for 7H6 and ZO-1 was performed in liver sections. In control rats, immunostaining for 7H6 and ZO-1 colocalized to the apical site of BECs and was continuous along the bile canaliculi. In GVHD, 7H6 expression was decreased in BECs and was discontinuous along the bile canaliculi. On the other hand, the intensity of ZO-1 staining in hepatocytes increased and did not change in BECs compared with that of control rats. Changes in TJ-associated proteins of both hepatocytes and BECs may reflect the immunopathogenesis of GVHD-associated intrahepatic cholestasis.
authors.affiliation: Second Department of Medicine, Kurume University School of Medicine, Japan. sasatomik@hotmail.com
authors.forename: Kurumi
authors.initials: K
authors.lastname: Sasatomi
authors.forename: Shotaro
authors.initials: S
authors.lastname: Sakisaka
authors.forename: Takumi
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hanada
authors.forename: Eitaro
authors.initials: E
authors.lastname: Taniguchi
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Masaru
authors.initials: M
authors.lastname: Harada
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D002780:Cholestasis, Intrahepatic / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C089734:antigen 7H6