2004 Fiscal Year Final Research Report Summary
Identification and characterization of the phenotype of hepatic stem cells in various liver diseases, its application to frontier medicine
| Project/Area Number |
14370068
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kobe University |
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Principal Investigator |
HAYASHI Yoshitake Kobe University, School of Medicine, Professor, 医学部, 教授 (50189669)
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| Co-Investigator(Kenkyū-buntansha) |
GU Eisei Kobe University, School of Medicine, Professor, 医学部, 教授 (40195615)
SEO Yasushi Kobe University, Grad Sch. Medicine, Assistant, 大学院・医学系研究科, 助手 (90362772)
KANOMATA Naoki Kobe University Hospital, School of Medicine, Assistant, 医学部附属病院, 助手 (60263373)
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| Project Period (FY) |
2002 – 2004
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| Keywords | HNF / Oval cell / Hepatocellular carcinoma / Regeneration / Stem cell / Hepatic stemcell / Fatty change of liver / Nonalcoholic steatohepatitis (NASH) |
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| Research Abstract |
During regeneration of liver tissue, oval cells which don't die by apoptosis, induces apoptosis in surrounding hepatocytes. Administration of 2-acetylaminofluorene (2-AAF) followed by partial hepatectomy causes proliferation of oval cell in rats. Caspase-3, Fas, Fas-L and Bax expressed in hepatocytes, but not in oval cells. This may be the molecular mechanism that the oval cells, without any damage in itself, induce apoptosis of surrounding hepatocytes (J Gastroenterol Hepatol19(8) :866-872, 2004). Diethylnitrosamine (DEN) was given to same animal model before administration of 2-AAF to induce hepatocellular carcinom to estimate the efficacy of INF-alpha for prevention of HCC (Carcinogenesis 25(3) :389-397, 2004). Alteration of iver-enriched nuclear protein and signal transduction related to fat-droplets in hepatocytes is also involving the differentiation of liver and pancreatic cell, and onset of diabetes. The report that the activation of protein kinase C is related to fatty changes of liver and insulin-sensitivity (J Clin Investigation 112:935-944, 2003). The protein p27(Kip1) regulates cell cycle progression in mammals by inhibiting the activity of cyclin-dependent kinases (CDKs). We show that p27(Kip1) progressively accumulates in the nucleus of pancreatic beta cells in mice that lack either insulin receptor substrate 2 (Irs2(-/-)) or the long form of the leptin receptor (Lepr(-/-) or db/db). p27(Kip1) contributes to beta-cell failure during the development of type 2 diabetes in Irs2(-/-) and Lepr(-/-) mice and represents a potential new target for the treatment of this condition. (Nature Medicine ll(2):175- 182, 2005).
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