2020 Fiscal Year Final Research Report
JAK2V617F mutation promotes chronic hypoxia-induced pulmonary hypertension in mice.
Project/Area Number |
19K17609
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | Fukushima Medical University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2021-03-31
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Keywords | 肺高血圧症 / JAK2V617F / 骨髄増殖性疾患 |
Outline of Final Research Achievements |
Pulmonary hypertension (PH) is one of major complications of hematological diseases such as myeloproliferative neoplasms (MPNs). An acquired mutation of JAK2V617F is causally related with MPNs including polycythemia vera, essential thrombocythemia and myelofibrosis. However, the role of JAK2V617F on PH remains unclear. We used the transgenic mice expressing JAK2V617F. JAK2V617F mice and WT mice were exposed continuous hypoxia (10% O2) for 2 weeks to induce PH. Controls were bred under normoxia. Although hypoxia significantly increased RVSP in both JAK2V617F mice and WT mice compared to the normoxic groups, RVSP in JAK2V617F mice was significantly higher than those in WT mice after hypoxia. Elastica-Masson staining demonstrated that the medial wall thickening of pulmonary arteries was significantly increased in hypoxia-exposed JAK2V617F mice compared to hypoxia-exposed WT mice. MPNs caused by JAK2V617F is associated with development of PH by remodeling of pulmonary arteries in mice.
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Free Research Field |
循環器内科学
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Academic Significance and Societal Importance of the Research Achievements |
本研究により、JAK2V617変異を有する肺高血圧症患者において、JAK/STAT経路の活性を制御できれば新たな肺高血圧症治療のターゲットになり得るものと期待される。
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