The protective role of Nrf2 in the development of acute lung injury and pulmonary fibrosis
| Project/Area Number |
18590836
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ISHII Yukio University of Tsukuba, Graduats School of Comprehensive Human Sciences, Assistant Professor (80272194)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Transcription factors / Nrf2 / Acute lung injury / Pulmonary fibrosis / Oxidative stress / Macrophages / Nrf2 / マクロファージ / 急性肺傷害 / 炎症 |
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| Research Abstract |
Oxidative stress may play an important role in the pthogenesis of acute lung injury and pulmonary fibrosis. Transcription factor Nrf2 counteracts oxidative tissue damage and inflammation through transcriptional activation via the antioxidant responsive element (ARE). To clarify the protective role of Nrf2 in the development of acute lung injury and pulmonary fibrosis, bleomycin was administrated to both C57BL/6 wild-type (WT) mice and Nrf2-knockout (Nrf2-/-) mice of the same background. The survival rate after bleomycin treatment was significantly decreased in Nrf2-/-mice compared with WT mice. The degree of acute lung injury, indicated by albumin concentration and the number of neutrophils in bronchoalveolar fluids, was much higher in Nrf2-/-mice than in WT mice 1 and 3 days after bleomycin administration. The degree of pulmonary fibrosis was also much greater in Nrf2-/-mice than in WT mice 28 days after bleomycin administration. The expression of antioxidant and phase 2 enzymes was inducible in the lungs of WT mice, but not in that of Nrf2-/- mice after bleomycin administration. Results indicated that Nrf2 protects against the development of acute lung injury and pulmonary fibrosis by lowering oxidative stress through regulating the expression of antioxidant molecules.
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Report
(3 results)
Research Products
(12 results)
