Pathophysiological analysis of thrombosis using genetically engineered mouse models

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09835
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Japan Women's University (2018); Koriyama Women's University (2016-2017)
• Principal Investigator: BANNO FUMIAKI 日本女子大学, 家政学部, 講師 (00373514)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 血栓症モデルマウス / プロテインS / プラスミノーゲン / ADAMTS13 / インテグリン

Outline of Final Research Achievements

In this study, we analyzed the effects of thrombotic molecules and their gene mutations on the pathogenesis of thrombosis using genetically modified mice established so far. The coexistence of the plasminogen-A622T mutation did not aggravate the thrombotic tendency caused by the protein S-K196E mutation. ADAMTS13 suppressed excessive neutrophil infiltration in the innate immune response. Extracellular signal-regulated kinase in platelets was essential for initiation and maintenance of thrombus formation. Protein kinase A in platelets inhibited thrombus formation only in the early phase. The integrin αIIb-R990W mutation induced constitutive activation of αIIbβ3 on platelets, but simultaneously reduced the expression of αIIbβ3 to cause impaired platelet aggregation.

Free Research Field

血栓止血学、生化学

Academic Significance and Societal Importance of the Research Achievements

血栓症に関わる分子やその遺伝子変異の病態生理学的意義が明らかとなり、血栓症治療の充実につながる成果が得られた。