論文

査読有り 国際誌
2009年2月

Matrix proteins of basement membrane of intrahepatic bile ducts are degraded in congenital hepatic fibrosis and Caroli's disease.

The Journal of pathology
  • Mitsue Yasoshima
  • ,
  • Yasunori Sato
  • ,
  • Shinichi Furubo
  • ,
  • Kazuo Kizawa
  • ,
  • Takahiro Sanzen
  • ,
  • Satoru Ozaki
  • ,
  • Kenichi Harada
  • ,
  • Yasuni Nakanuma

217
3
開始ページ
442
終了ページ
51
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/path.2472
出版者・発行元
JOHN WILEY & SONS LTD

Congenital hepatic fibrosis (CHF) and Caroli's disease are though to result from ductal plate malformation, and the basal laminar components play important roles in biliary differentiation during development. To clarify the involvement of basal laminar components in the ductal plate malformation, this study examined the immunohistochemical expression of laminin and type IV collagen in the livers of CHF and Caroli's disease. Using the polycystic kidney (PCK) rat, an animal model of Caroli's disease with CHF, in vivo and in vitro experiments were also performed. Immunostaining showed that basement membrane expression of laminin and type IV collagen around intrahepatic bile ducts was degraded in CHF, Caroli's disease, and the PCK rats. The degradation of laminin and type IV collagen around bile ducts was also observed in foci of cholangiocarcinoma in situ of Caroli's disease. In vitro, PCK cholangiocytes were found to overexpress plasminogen and a serine proteinase, the tissue-type plasminogen activator (tPA). When PCK cholangiocytes were cultured in Matrigel, the amounts of laminin and collagen in the gel were significantly reduced, and addition of alpha2-antiplasmin in the culture medium inhibited the degradation of laminin and collagen in Matrigel. These results suggest that biliary overexpression of plasminogen and tPA leads to the generation of excessive amounts of plasmin, and subsequent plasmin-dependent lysis of the extracellular matrix molecules may contribute to the biliary dysgenesis in CHF and Caroli's disease, including progressive cystic dilatation of the intrahepatic bile ducts in Caroli's disease. In addition, it is suggested that once cholangiocarcinoma in situ develops in the biliary epithelium of CHF and Caroli's disease, it tends to transform into invasive carcinoma, due to instability of the basement membrane of the bile ducts.

リンク情報
DOI
https://doi.org/10.1002/path.2472
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19025978
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000263076900012&DestApp=WOS_CPL
ID情報
  • DOI : 10.1002/path.2472
  • ISSN : 0022-3417
  • PubMed ID : 19025978
  • Web of Science ID : WOS:000263076900012

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