title: Aberrant expression of claudin-4 and -7 in hepatocytes in the cirrhotic human liver.
abstract: The liver comprises hepatocytes and non-parenchymal cells such as bile duct epithelial cells. Claudin-4 and -7 are not expressed in hepatocytes under physiological conditions. It was reported that claudin-7 increased in human pulmonary fibroses. We therefore investigated claudin-4 and -7 expressions in human cirrhotic livers, in which hepatocyte proliferation is severely delayed. We examined liver tissues from 50 patients with liver tumors. The expression of claudin-4 and -7 in hepatocytes significantly increased with the grade of fibrosis, not with inflammatory activity, in the liver tissues of chronic hepatitis. The number of claudin-4- and -7-positive cells observed was greater than that of alpha-fetoprotein-positive hepatic progenitor cells. In primary cultures of mouse hepatocytes, the expression of claudin-4 and -7 was not induced by treatment with proinflammatory cytokines. In immunohistochemical analysis of liver tissues of 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated mice and primary cultures of mouse hepatocytes, the expression of claudin-4 and -7 increased with proliferation of progenitor cells. However, the claudin-4- and -7-positive cells were not always progenitor cells. Thus, claudin-4 and -7 were observed in hepatocytes of severely damaged mouse and human livers. These findings suggest that claudin-4- and -7-positive hepatocytes may exist during the process of differentiation from progenitor cells into mature hepatocytes.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, S1. W17, Sapporo, 060-8556, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tsujiwaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Murata
authors.forename: Akira
authors.initials: A
authors.lastname: Takasawa
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Hiratsuka
authors.forename: Rieko
authors.initials: R
authors.lastname: Fukuda
authors.forename: Kotaro
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ono
authors.forename: Masanori
authors.initials: M
authors.lastname: Nojima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sawada
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D062506:Claudin-4 / Q000096:biosynthesis*; D057167:Claudins / Q000096:biosynthesis*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D053683:Oncostatin M / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C473255:CLDN7 protein, human; D062506:Claudin-4; D057167:Claudins; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M
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