Molecular pathophysiology of pulmonary fibrosis in oxygen poisoning
| Project/Area Number |
22590630
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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 |
Legal medicine
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| Research Institution | University of Fukui |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MATUKI Takasumi 福井大学, 医学部, 教授 (10126617)
MATUI Kazuhiro 福井大学, 医学部, 客員教授 (80181676)
伊藤 慎治 九州大学, 医学部, 学術研究員 (30570585)
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| Co-Investigator(Renkei-kenkyūsha) |
YASUDA Toshihiro 福井大学, 医学部, 教授 (80175645)
IMAMURA Yoshiaki 福井大学, 医学部附属病院, 准教授 (40223341)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 瀰漫性肺胞傷害 / 高濃度酸素曝露 / 低酸素濃度曝露 / アポトーシス / c-Myc(Myelocytomatosis oncogene) / CTGF(Connective tissue growth factor) / 肺サーファクタント蛋白 / リゾチーム / c-Myc / CTGF / 瀰慢性肺胞傷害 / インターロイキン6 / Galectin-3 |
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| Research Abstract |
Eight-week-old mice (C57BL/6J) were bred as follows. In the 100 % oxygen-exposure experiment, the parameters were duplicated. Twenty male mice weighing 21-24 g were randomly divided into four groups as follows: (1) five mice for the control group were kept in atmospheric oxygen; (2) another fifteen mice to be used as the hyperoxia-exposure group were kept in a metallic chamber for 1 day, 2 days, and 3 days, respectively, into which oxygen flowed at a rate of 0.8 liter / min. The oximeter (JKO-25LJII, JIKCO Ltd, Japan), which was connected with the chamber, indicated 95-100 % oxygen concentration. In the 75 % oxygen-exposure experiment, ten male mice were randomly divided into two groups as follows: (1) five mice for the control group were kept in atmospheric oxygen; (2) another five mice to be used as the hyperoxia-exposure group were kept in a metallic chamber for 9 days, respectively.In the 60 % oxygen- and 40 % oxygen-exposure experiments, ten male mice were randomly divided into tw
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o groups as follows: (1) five mice for the control group were kept in atmospheric oxygen; (2) another five mice to be used as the hyperoxia-exposure group were kept in a metallic chamber for 4 weeks, respectively. In the 6 % oxygen-exposure experiment, ten male mice were randomly divided into two groups as follows: (1) five mice for the control group were kept in atmospheric oxygen; (2) another five mice to be used as the hypoxia-exposure group were kept in a metallic chamber for 3 days, respectively. In these experiment, we could not establish marked pulmonary fibrosis in mice. We have already elucidated transcript profiling of diffuse alveolar damage (DAD) induced by hyperoxia exposure in mice and showed that the mRNA level of surfactant-associated protein C (SP-C) is significantly down-regulated, while that of c-Myc is significantly up-regulated (Int J Legal Med 2008;122:373-83). To confirm the molecular pathophysiology of this alveolar dysfunction more precisely, other surfactant-associated genes and apoptosis-related genes were examined in this Grants-in-Aid for Scientific Research (C). Our study showed that: (1) hyperoxia induces a marked increase in protein levels of 4-hydroxy-2-nonenal (HNE)-amino acid Michael adduct and c-Myc; and (2) mRNA levels of surfactant-associated protein A (SP-A) and surfactant-associated protein C (SP-C) are significantly down-regulated, while those of c-Myc and Bax are significantly up-regulated in hyperoxia exposure. These results suggest that: (1) c-Myc and Bax overexpression means progression of apoptosis, which brings about a malignant cycle of reactive oxygen species (ROS) production; and (2) multiple apoptotic pathways seem to be involved in decreases in levels of mRNAs for SP-A and SP-C, in turn causing the serious risk for pulmonary collapse. Less
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Report
(4 results)
Research Products
(8 results)
