| Project/Area Number |
18K16168
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Hiroyoshi Mori 国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (00794330)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Arid5a / 肺高血圧症 / 慢性炎症 / サイトカイン / 炎症 |
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| Outline of Final Research Achievements |
Pulmonary hypertension is a refractory disease which cause stenotic and occlusive lesions in the pulmonary arteries, leading to elevated pulmonary arterial pressure and right heart failure. It has been reported that inflammation is an important factor in the pathogenesis of pulmonary hypertension. In this study, we focused on Arid5a, a protein which regulates inflammation by stabilizing mRNA of inflammation related genes. We constructed a pulmonary hypertension model using genetically modified mice and investigated the significance of Arid5a in the pathogenesis of pulmonary hypertension. Hemodynamic analysis revealed that the phenotype of pulmonary hypertension was attenuated in Arid5a-deficient mice. In addition, it was suggested that the composition of immune cells and the gene expression of vascular cells might be altered.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によりArid5aが肺高血圧症の病態に関与していることが明らかとなった。mRNAの安定化に寄与する蛋白質が肺高血圧症の新たな治療標的となりうることを示したものであり、今後の新規治療薬創出の観点から意義のある成果である。
さらに、これまでは主に免疫細胞におけるArid5aの重要性が報告されてきたが、今回の研究では、肺高血圧症の病態形成においてArid5aは血管構成細胞においても重要な役割を果たしていることが示唆された。非免疫細胞におけるmRNAの安定化と疾患との関わりを示すものであり、学術的にも意義のある成果と言える。
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