| Project/Area Number |
16209038
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Nihon University |
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Principal Investigator |
TAKAYAMA Tadatoshi Nihon University, School of Medicine, Professor, 医学部, 教授 (30280944)
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| Co-Investigator(Kenkyū-buntansha) |
MAKUUCHI Masatoshi The University of Tokyo, School of Medicine, Professor, 医学部附属病院, 教授 (60114641)
INOUE Kazuto Nihon University, School of Medicine, Associate Professor, 医学部, 助教授 (00372996)
YAMAZAKI Shintaro Nihon University, School of Medicine, Research Associate, 医学部, 助手 (20409014)
渡辺 善広 日本大学, 医学部, 講師 (20240533)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000)
Fiscal Year 2006: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2005: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2004: ¥22,360,000 (Direct Cost: ¥17,200,000、Indirect Cost: ¥5,160,000)
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| Keywords | liver regeneration / bone marrow stem cell / Transdifferentiation / chemokine / gene chip |
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| Research Abstract |
Background/Aims: Bone marrow cells are highly plastic and differentiate into various cell types, including hepatocytes. To explore the mechanisms underlying these processes, we focused on the initial responses of bone marrow to hepatectomy, using a mouse model.
Methods: To evaluate hepatic differentiation in bone marrow cells we measured hepatocyte-related gene expression in mice undergoing partial hepatectomy with or without pretreatment for 1 week with 2-acetyl aminofluorene (AAF).
Results: Hepatectomy induced several genes related to early hepatic differentiation in bone marrow. Expression of these genes was enhanced by the administration of AAF, whereas genes specific for mature hepatocytes were not detected. We characterised the bone marrow cell population expressing hepatocyte differentiation genes. a-fetoprotein mRNA was induced in Lin-and either CD34+, c-kit+, Sca-1+, CD49f+ or CD45+ cells. The genes upregulated in the liver after AAF treatment and hepatectomy were identified using oligonucleotide microarrays. These included genes associated with the acute phase response. Dexamethasone inhibited the expression of early hepatic differentiation genes in the bone marrow of AAF/PHx mice.
Conclusions: Early hepatic differentiation genes were induced in bone marrow in response to hepatectomy, especially when regeneration of the remnant liver was suppressed. Circulating signals generated in the AAF/PHx liver might activate this differentiation.
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