| Project/Area Number |
25461154
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Mie University |
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Principal Investigator |
Taguchi Osamu 三重大学, 保健管理センター, 教授 (90197244)
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| Co-Investigator(Kenkyū-buntansha) |
Gabazza Esteban 三重大学, 医学系研究科, 教授 (00293770)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肺高血圧症 / RNA干渉 / 転写因子 / ペリオスチン / 肺線維症 / 慢性閉塞性肺疾患 / 肺気腫 / 核酸 / ＮＦkappaB / ＥＴ-１ / 難病 / off-target / 内皮細胞障害 / エンドセリン受容体 / エンドセリン / 炎症 / 核酸siRNA干渉 / エントセリン / エントセリンレセプター / 動物モデル / モノクロタリン / サイトカイン |
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| Outline of Final Research Achievements |
Pulmonary hypertension may be of unknown etiology or caused by underlying disorders including emphysema, lung fibrosis or thromboembolism. This study evaluated the usefulness of RNA interference against NF-kappaB and periostin for pulmonary hypertension associated with lung fibrosis and emphysema. Cigarette smoke extract significantly increased the expression of endothelin and its receptors in pulmonary epithelial cells. Mice with emphysema was treated with siRNA against NF-kappaB. Alveolar wall destruction and lung inflammation were significantly suppressed by NF-kappaB siRNA compared to untreated mice. In addition, periostin siRNA significantly inhibited the development of fibrosis compared to control RNA. Overall, the results of this investigation clearly demonstrated the usefulness of siRNA therapy against transcription factor and matrix protein for the treatment of diseases that frequently lead to the development of pulmonary hypertension.
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