Aberrant expression of claudin-4 and -7 in hepatocytes in the cirrhotic human liver

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• 作者：Mitsuhiro Tsujiwaki (1)
  Masaki Murata (1)
  Akira Takasawa (1)
  Yutaro Hiratsuka (1)
  Rieko Fukuda (1)
  Kotaro Sugimoto (1)
  Yusuke Ono (1)
  Masanori Nojima (2)
  Satoshi Tanaka (1)
  Koichi Hirata (3)
  Takashi Kojima (4)
  Norimasa Sawada (1)
  
  1. Department of Pathology ; Sapporo Medical University School of Medicine ; S1. W17 ; Sapporo ; 060-8556 ; Japan
  2. Division of Advanced Medicine Promotion ; The Advanced Clinical Research Center ; The Institute of Medical Science ; The University of Tokyo ; Tokyo ; Japan
  3. Department of Surgery ; Sapporo Medical University School of Medicine ; Sapporo ; Japan
  4. Department of Cell Science ; Research Institute of Frontier Medicine ; Sapporo Medical University School of Medicine ; Sapporo ; Japan
  
• 关键词：Claudin ; 4 ; Claudin ; 7 ; Hepatocyte ; Hepatitis ; Cirrhosis
• 刊名：Medical Molecular Morphology
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：48
• 期：1
• 页码：33-43
• 全文大小：10,970 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Medical Microbiology
  Pathology
  Biological Microscopy
  Molecular Medicine
  
• 出版者：Springer Japan
• ISSN：1860-1499

文摘

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.