| Project/Area Number |
18K07438
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Gunma University |
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Principal Investigator |
Endo Yukie 群馬大学, 大学院医学系研究科, 講師 (00372350)
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| Co-Investigator(Kenkyū-buntansha) |
茂木 精一郎 群馬大学, 大学院医学系研究科, 教授 (20420185)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 老化 / 早老症 / ラミンA / 線維化 / ウエルナー症候群 / Werner症候群 / ラミンＡ |
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| Outline of Final Research Achievements |
Werner syndrome is a "premature aging syndrome" in which signs of aging appear after puberty. Atypical Werner syndrome, which is also a form of premature aging syndrome, is characterized by skin sclerosis and lipoatrophy, Werner syndrome-like symptoms, and genetic mutations in the nuclear membrane protein lamin A. In this study, we have attempted to elucidate the mechanism of skin sclerosis and lipoatrophy using fibroblasts and adipocytes from patients with Atypical Werner syndrome, and new results are being obtained. On the other hand, mTOR inhibitors and farnesyltransferase inhibitors, which have been shown to be effective in Hutchinson-Gilford syndrome-derived cells, also caused by lamin A mutation, did not show any significant improvement.
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| Academic Significance and Societal Importance of the Research Achievements |
Atypical Werner症候群患者由来皮膚線維芽細胞では、同じくラミンＡ遺伝子変異が原因であるHutchinson-Gilford syndrome (HGS)の細胞様の核変形が多くみられ、ヘテロクロマチンの局在異常もみられた。さらに、健常人由来線維芽細胞と比べて、患者由来線維芽細胞では、酸化ストレスによる老化が亢進するだけではなく、UVA照射による光老化も亢進することを見出した。本研究の成果によって、さらに線維化と脂肪萎縮の機序を明らかにすることができれば、早老症における皮膚硬化の病態解明や新たな治療法の開発に貢献できると予想される。
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