2016 Fiscal Year Final Research Report
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 |
Research Field |
Pathological medical chemistry
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Research Institution | Kyushu University |
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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Keywords | 肝臓 / 再生 / 癌 / 細胞分化 |
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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Free Research Field |
発生学、再生医学、腫瘍学
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