2017 Fiscal Year Final Research Report
The pathology of thrombotic microangiopathy induced by liver specific Brat mutation
Project/Area Number |
16K14615
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Tumor biology
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Research Institution | Japanese Red Cross Hokkaido college of Nursing |
Principal Investigator |
Yamazaki Kohsuke 日本赤十字北海道看護大学, 看護学部, 教授 (20281884)
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Research Collaborator |
Tanaka Hiroki
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Project Period (FY) |
2016-04-01 – 2018-03-31
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Keywords | 肝癌 / TMA |
Outline of Final Research Achievements |
The Braf mutation plays a pivotal role in hepatocarcinogenesis. The liver of transgenic mice with a hepatocyte-specific human BRAFV600E mutation was entirely consisted of preneoplastic hepatocytes. These transgenic mice died due to thrombotic microangiopathy (TMA). This study was aimed to clarify the causes of TMA. Blood/tissue specimens collected from the transgenic mice were analysed haematologically/pathologically. In the transgenic mice, the liver showed thrombopoietin (TPO) overexpression, which is associated with thrombocytosis, and platelets were activated in hepatic sinusoids. Podoplanin was expressed in the Kupffer cells in the liver of the transgenic mice, indicating that platelet activation occurred via the interaction of podoplanin. TPO overproduction by BRAFV600E-mutated hepatocytes may contribute to thrombocytosis, platelet activation, while TMA due to aberrant platelet activation led to spontaneous death in some of the transgenic mice.
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Free Research Field |
腫瘍病理学
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