Hepaocyte injury induced by iron overload and its application for isolation of bile duct cells and stem cells
| Project/Area Number |
25670186
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 鉄 / 肝傷害 / 肝細胞 / 胆管上皮細胞 / 肝幹細胞 |
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| 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.
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Report
(3 results)
Research Products
(39 results)
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[Journal Article] Contributions of hepatocytes and bile ductular cells in ductular reactions and remodeling of the biliary system after chronic liver injuries.2014
Author(s)
Nagahama Y, Sone M, Chen X, Okada Y, Yamamoto M, Xin B, Matsuo Y, Komatsu M, Suzuki A, Enomoto K, Nishikawa Y.
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Journal Title
Am J Pathol
Volume: 184
Issue: 11
Pages: 3001-3012
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Loss of liver E-cadherin induces sclerosing cholangitis and promotes carcinogenesis.2014
Author(s)
Nakagawa H, Hikiba Y, Hirata Y, Font-Burgada J, Sakamoto K, Hayakawa Y, Taniguchi K, Umemura A, Kinoshita H, Sakitani K, Nishikawa Y, Hirano K, Ikenoue T, Ijichi H, Dhar D, Shibata W, Akanuma M, Koike K, Karin M, Maeda S.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 111
Issue: 3
Pages: 1090-1095
DOI
Related Report
Peer Reviewed
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[Journal Article] Tumor necrosis factor-α promotes bile ductular transdifferentiation of mature rat hepatocytes in vitro.2013
Author(s)
Nishikawa Y, Sone M, Nagahama Y, Kumagai E, Doi Y, Omori Y, Yoshioka T, Tokairin T, Yoshida M, Yamamoto Y, Ito A, Sugiyama T, Enomoto K.
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Journal Title
J Cell Biochem
Volume: 114
Issue: 4
Pages: 831-843
DOI
NAID
Related Report
Peer Reviewed
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