Molecular mechanisms of regulation of endothelial differentiation in cardiovascular morphogenesis and pathogenesis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09598
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Iwata Yuko 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (80171908)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 線維化抑制

Outline of Final Research Achievements

In order to clarify the physiological and pathological roles of the protein whose function is not known in cardiovascular morphogenesis and pathological conditions, we investigated one of the mechano-sensitive ion transporters with a high possibility of its interaction. We found a method to activate the mechano-sensitive ion transporter and identified inhibitors. In addition, an inhibitory antibody was produced and the epitope was identified. To elucidate the role of ion transporters in endothelial differentiation, we examined the effect of the inhibitory antibodies on endothelial mesenchymal transition. The inhibitory antibody treatment suppressed the metastasis of lung cancer induced by intravenously injecting highly metastatic myeloma cells to mice and the cardiac fibrosis in cardiomyopathic animal models. These experiments revealed that this ion transporter plays an important role in endothelial differentiation.

Free Research Field

分子生理学

Academic Significance and Societal Importance of the Research Achievements

内皮分化は形態形成だけでなく病態進展においても重要な働きをしている。イオン輸送体特異的阻害抗体を作成し、そのエピトープを同定した。この阻害抗体により、癌転移、心筋症線維化が抑制されたことは、このイオン輸送体が病態進展に重要な働きをしていることを示唆しており、病態治療への一助となると思われる。