| Project/Area Number |
25293166
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General internal medicine(including psychosomatic medicine)
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| Research Institution | Nagoya Women's University (2015-2016)
Nagoya University (2013-2014) |
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Principal Investigator |
isobe ken-ichi 名古屋女子大学, 家政学部, 教授 (20151441)
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| Co-Investigator(Kenkyū-buntansha) |
祖父江 元 名古屋大学, 医学(系)研究科(研究院), 教授 (20148315)
大橋 憲太郎 岐阜大学, 工学部, 准教授 (50332953)
伊藤 佐知子 名古屋大学, 医学(系)研究科(研究院), 助教 (70447845)
西尾 尚美 名古屋大学, 医学(系)研究科(研究院), 助教 (80513457)
長谷川 忠男 名古屋市立大学, 医学(系)研究科(研究院), 教授 (10314014)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
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| Keywords | 老化 / GADD34 / ERストレス / ２型糖尿病 / 脂肪肝 / インスリンシグナル / メタボリックシンドローム / ストレス / 生活習慣病 / 免疫 / 再生 |
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| Outline of Final Research Achievements |
We intended to analyze age-related disease from the points of ER stresses and immune responses. Acrolein, which is abundant in cigarette smoke, and cooking emission,
plays a major role in COPD . Acrolein induced the expression of GADD34 and acute inflammation in airways, which followed COPD. Acrolein-induced phosphorylation of eIF2α in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. We examine the effects of GADD34 on natural life span by using GADD34-deficient mice. We found that with age GADD34-deficient mice become obese, developing fatty liver followed by liver cirrhosis, hepatocellular carcinoma, and insulin resistance. GADD34 suppresses insulin signaling in young mice. However, by aging macrophages in fat tissues work to induce insulin resistance. We succeeded to differentiate to various tissue cells from iPSCs established from aged mice, which may repair damaged tissues by age-related diseases.
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