| Project/Area Number |
20590925
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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 | Ehime University |
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Principal Investigator |
OGASAWARA Masato Ehime University, 大学院・医学系研究科, 准教授 (00325367)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Saho 愛媛大学, 大学院・医学系研究科, 助教 (10301326)
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| Research Collaborator |
YAMAUCHI Kohei 岩手医科大学, 医学部, 教授
OOGUSHI Fumitaka 国立病院機構, 高知病院, 院長
TAKAHASHI Saori 秋田県総合食品研究センター, 食品加工研究所, 所長
NIRASAWA Satoru 独立行政法人農業・食品産業技術総合研究所, 食品バイオテクノロジー研究領域酵素研究ユニット, 主任研究員
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 間質性肺炎 / 異性体化蛋白質 / 上皮間葉移行 / 小胞体ストレス / 上皮-間葉系移行 / 異性体化たんぱく質 / 肺線維症 / 蛋白質異性体化 / 上皮-間葉系移行(EMT) / 異性体アミノ酸 |
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| Research Abstract |
Heat shock proteins are involved in the pathogenesis of idiopathic interstitial pneumonia, when misfolded proteins as a consequence of genetic mutations are generated. Although genome wide investigations have been performed, genetic mutations have not been identified in idiopathic interstitial pneumonia. We focused on isomerization and racemization of aspartic acid in the proteins during aging and oxidative stress, which can change three dimensional structure and induce stress proteins productions. In the cells, protein isomerization and racemization repair enzyme (PCMT1) exists for recovery and recycle of the partially damaged proteins. An alveolar epithelial cell line, A549, was subjected to epithelial-to-mesenchymal transition that was caused by PCMT1 gene knock down transfected with shRNA vector. The endoplasmic reticulum stress marker protein, GRP78, was induced after transfection. On the other hand, TGF β1, which is a potent inducer of fibrosis in the lung, could not induce GRP78, rather decreased expression. The expression of PCMT1 with TGF β1 treatment was comparable with the value found by PCMT1-shRNA vector transfection. The current study indicated that the novel molecular mechanism by accumulation of isomerized and racemized misfolded proteins seems to be one of causes of idiopathic interstitial pneumonia.
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