| Project/Area Number |
17K19917
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Health science and related fields
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| Research Institution | Nagasaki University |
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Principal Investigator |
MORI Ryoichi 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30509310)
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| Co-Investigator(Kenkyū-buntansha) |
鳥越 秀峰 東京理科大学, 理学部第一部応用化学科, 教授 (80227678)
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| Research Collaborator |
SHIMOKAWA Isao
KOMATSU Toshimitsu
TANAKA Katsuya
NOZAKI Tadashige
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | microRNA / NAFLD / NASH / アンチセンスオリゴ / 脂肪肝 / 寿命 / 代謝 / 老化 / miRNA / 肝臓 / 遺伝子 / 細胞・組織 / トランスレーショナルリサーチ / 病理学 / 免疫学 |
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| Outline of Final Research Achievements |
Compared with wild-type (WT) mice, miR-X KO mice have shorter life spans (median survival time 117 and 54 weeks for WT and KO mice, respectively), which was extended by feeding a high-fat diet (HFD) (96 and 72 weeks, respectively). WT mice exhibited age-related fatty liver disease; however, this was attenuated by miR-X deficiency mice. Moreover, HFD feeding protected miR-X KO mice from the hepatic steatosis observed in age-matched HFD-fed WT mice, suggesting that miR-X plays a key role in hepatic lipid metabolism.
Candidate miR-X target mRNAs were identified by performing RNA-sequencing of livers from 54-week-old WT and miR-X KO mice. We identified 2,245 genes that were upregulated (>2.0-fold) in miR-X KO livers compared with WT livers. Among these genes, bioinformatic analysis revealed seven candidate miR-X target mRNAs that were markedly associated with biological pathways in lipid metabolism.
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| Academic Significance and Societal Importance of the Research Achievements |
食生活の変化に伴って、脂肪肝を呈する日本人は急増している。脂肪肝が悪化すると NAFLD・NASH へと進展するため、新たな治療薬及び検査マーカーの創出が急務である。臓器線維化は、不可逆的反応である。NASH では高度な線維化を伴うため、発症を事前に防ぐことも重要である。本研究達成により、miR-X が関与する脂肪肝発症及び NASH へと進展するメカニズム、そして miR-X を標的としたアンチセンスオリゴ（核酸医薬）の開発に成功した。miR-X を治療標的・検査マーカー分子として位置づけることにより先制医療確立に貢献していきたいと考えている。
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