| Project/Area Number |
16H05203
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | Tokyo University of Science (2018)
The University of Tokyo (2016-2017) |
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Principal Investigator |
Matsushima Kouji 東京理科大学, 研究推進機構生命医科学研究所, 教授 (50222427)
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| Co-Investigator(Kenkyū-buntansha) |
橋本 真一 金沢大学, 医薬保健学総合研究科, 特任教授 (00313099)
上羽 悟史 東京理科大学, 研究推進機構生命医科学研究所, 准教授 (00447385)
島岡 猛士 東京理科大学, 研究推進機構生命医科学研究所, 助教 (90422279)
七野 成之 東京理科大学, 研究推進機構生命医科学研究所, 助教 (70822435)
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| Research Collaborator |
Nakajima Takuya
Aoki Hiroyasu
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 肺線維症 / 転写因子 / 線維芽細胞 / トランスクリプトーム / 線維症 / 脂質代謝 |
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| Outline of Final Research Achievements |
Activated lung fibroblasts play important roles in the pathogenesis of pulmonary fibrosis by acting as major producers of extracellular matrix components. However, the regulatory mechanisms of fibroblast responses during PF progression remain elusive. To address these questions, we purified lung fibroblasts from fibrotic murine lungs at multiple time points, and performed global transcriptome analysis. We identified genes of which expression kinetics was associated with the pathological course of PF. Next, we identified 17 hub transcription factors, including Srebf1/LXR, as novel candidates that may contribute to lung fibroblast activation and PF pathology. We confirmed that modulation of Srebf1/LXR suppressed the activation state of lung fibroblasts and PF pathology. Collectively, our data provide novel insights into the transcriptional dynamics of fibroblasts during PF progression and suggests that lipid metabolism might contribute to lung fibroblast activation and PF pathology.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、肺線維化病態における線維芽細胞の転写制御ネットワークの実体と、その中心となるハブ転写因子群が新たに同定された。肺線維芽細胞は脂肪滴を豊富に有していることが知られているが、本研究の成果はそれらの生理的意義を示唆したという点で学術的意義がある。また、LXRアゴニストの肺線維症治療効果が認められたことから、LXR-Srebf1経路は新たな肺線維症の治療標的になりうるという観点で、社会的意義を有すると言える。
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