Project/Area Number |
22590859
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
|
Research Institution | Mie University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
TAGUCHI Osamu 三重大学, 医学系研究科, 准教授 (00293770)
田口 修 三重大学, 医学(系)研究科(研究院), 准教授 (90197244)
|
Project Period (FY) |
2010 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 肺線維症 / siRNA / RNAi / TGF-β / リモデリング / 線維芽細胞 |
Research Abstract |
SiRNA has been the focus of attention for its potential application for the development of new drugs.To evaluate the effect of intratracheal administration of siRNAs in murine disease models. Firstly, bleomycin was used for induction of lung fibrosis. After confirming the effectiveness of siRNA effect in vitro, siRNAs for several targets including TGF-beta1 were intratracheally administered by inhalation. Mice treated with scrambled siRNA or vehicle were used as controls. We generated a novel model of human TGF-beta1 transgenic mouse that spontaneously develops pulmonary fibrosis. Intrapulmonary delivery of aerosolized siRNAs of TGF-beta1 significantly inhibited bleomycin-induced pulmonary fibrosis. In addition, aerosolized siRNAs against human TGF-beta1 also inhibited spontaneous pulmonary fibrosis.These results suggest that intratracheal instillation of RNAi agents may be useful for the therapy of airway remodeling.
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