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2014 Fiscal Year Final Research Report

Hepaocyte injury induced by iron overload and its application for isolation of bile duct cells and stem cells

Research Project

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Project/Area Number 25670186
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionAsahikawa Medical College

Principal Investigator

NISHIKAWA Yuji  旭川医科大学, 医学部, 教授 (90208166)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Masahiro  旭川医科大学, 医学部, 助教 (30431399)
FUJII Kiyonaga  旭川医科大学, 医学部, 助教 (10278327)
Project Period (FY) 2013-04-01 – 2015-03-31
Keywords鉄 / 肝傷害 / 肝細胞 / 胆管上皮細胞 / 肝幹細胞
Outline of Final Research Achievements

We previously experienced an autopsy case of fulminant liver failure due to acute excessive consumption of sodium ferrous citrate. The liver damage was characterized by complete sparing of bile duct cells despite the loss of almost all hepatocytes. In the present study, we investigated the mechanism of hepatocyte-specific injury induced by nontransferrin-bound iron using a mice model and tried to apply this iron-induced hepatocyte injury to the development of a highly specific isolation method of bile duct cells. In mice, oral administration of sodium ferrous citrate induced hepatocyte-specific injury associated with marked phosphorylation of JNK and c-Jun. Hepatocytes were found to be completely nonviable when they were isolated from mice treated with lethal doses of iron. However, bile duct cells within the Glisson’s sheath were intact and perfectly suited for culturing. This new method of pure isolation of bile duct cells may be useful in the studies of the biliary system.

Free Research Field

実験病理学

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Published: 2016-09-02  

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