Elucidation of molecular mechanisms connecting a breakdown of cellular differentiation to the pathogenesis of liver diseases
| Project/Area Number |
25713014
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kyushu University |
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Principal Investigator |
Suzuki Atsushi 九州大学, 生体防御医学研究所, 教授 (30415195)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000)
Fiscal Year 2015: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2013: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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| Keywords | 肝臓 / 再生 / 癌 / 細胞分化 |
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| Outline of Final Research Achievements |
Our previous studies demonstrated that hepatocytes could be converted into biliary lineage cells through activation of Notch signaling in liver diseases. In this study, we found that, in a mouse model of intrahepatic cholangiocarcinoma, hepatic macrophages called Kupffer cells express the Notch ligand Jagged-1 coincident with Notch activation in pericentral hepatocytes, and depletion of Kupffer cells prevents the Notch-mediated cell-fate conversion of hepatocytes to biliary lineage cells. Meanwhile, we also found that hepatic progenitor cells (HPCs), which arise from hepatocytes in a chronically injured liver, can give rise to myofibroblasts, in addition to hepatocytes and cholangiocytes, as descendants. During tumor development, HPCs can contribute to the formation of the tumor microenvironment by producing abundant myofibroblasts. These findings will be useful for uncovering the pathogenic mechanism of liver diseases and developing therapeutic strategies for such diseases.
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Report
(5 results)
Research Products
(64 results)
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[Journal Article] Transcription factors interfering with dedifferentiation induce cell type-specific transcriptional profiles.2013
Author(s)
Hikichi T, Matoba R, Ikeda T, Watanabe A, Yamamoto T, Yoshitake S, Tamura-Nakano M, Kimura T, Kamon M, Shimura M, Kawakami K, Okuda A, Okochi H, Inoue T, Suzuki A, Masui S.
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Journal Title
Proceeding of the National Academy of Sciences of USA
Volume: 110
Issue: 16
Pages: 6412-6417
DOI
NAID
Related Report
Peer Reviewed
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