The mechanisms of pulmonary hypertension in Down syndrome by iPSC technology
Project/Area Number |
17K16261
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Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
|
Research Institution | Osaka University |
Principal Investigator |
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | ダウン症候群 / 肺高血圧 / iPS細胞 |
Outline of Final Research Achievements |
It is well known that Down syndrome patients with congenital heart defects tend to progress pulmonary hypertension, however the moleccular mechanisms are unclarified until now. In this study, we established iPSCs from Down syndrome patients and differentiated them into vascular endotheial cells and vascular smooth muscle cells. Then we analyzed the cellular physiology and comprehensive gene expression profiling of these cells. We found that vascular smooth muscle cells of Down syndrome showed higher proliferative ability. We also found that endhothelial dysfunction with dysregulation of mitochondrial function, and gene expression patterns were significantly different in Down syndrome endothelial cells as compared to wild type controls.
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Academic Significance and Societal Importance of the Research Achievements |
本研究によって、ダウン症候群患者において肺高血圧が多くなる要因として、血管細胞機能が変化していることが判明した。特に内皮細胞におけるミトコンドリア機能障害が大きく寄与している可能性がある。さらに、内皮細胞の発現プロファイル解析から、21染色体以外の遺伝子においても特徴的な発現パターンを示している遺伝子が見つかった。これらの遺伝子の機能を解析することにより、新たな治療法の開発につながると考えられる。
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Report
(4 results)
Research Products
(3 results)