Clarification epigenetic regulatory mechanisms underlying ageing-related sarcopenia
| Project/Area Number |
19H03786
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Ehime University |
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Principal Investigator |
Imai Yuuki 愛媛大学, プロテオサイエンスセンター, 教授 (10423873)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Keywords | サルコペニア / 筋衛星細胞 / エピジェネティクス / Uhrf1 / Dnmt1 / 骨格筋 / DNAメチル化 |
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| Outline of Research at the Start |
健康長寿獲得のためには、要支援の最大要因であるサルコペニアなどの運動機能退行メカニズムの理解とその予防・治療法の開発が必須である。そのために遺伝的要因の同定と、老化などの環境因子を含めた後天的要因の理解が必要である。「後天的要因のエフェクターと考えられるエピゲノム変化の蓄積がいかに運動器の生理機能に寄与し、その破綻がどれほどサルコペニアなど運動機能の低下や進展に関与しているのか？」が本研究課題の学術的な「問い」である。加齢に伴い進展する運動機能低下、特に筋力低下（サルコペニア）の病態におけるエピゲノム制御因子の役割を明らかにすることで、筋力維持を目的とした新規治療標的分子の同定を目指す。
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| Outline of Final Research Achievements |
We demonstrate that a key epigenetic regulator, ubiquitin like with PHD and RING finger domains 1 (Uhrf1), is activated in proliferating myogenic cells but not expressed in quiescent satellite cells or differentiated myogenic cells in mice. Ablation of Uhrf1 or Dnmt1 in mouse satellite cells impairs their proliferation and differentiation, leading to failed muscle regeneration. Uhrf1-deficient myogenic cells exhibited aberrant upregulation of transcripts, including Sox9, with the reduction of DNA methylation level of their promoter and enhancer regions. These findings show that Uhrf1 and Dmt1 are critical epigenetic regulators of proliferation and differentiation in satellite cells, by controlling cell-type-specific gene expression via maintenance of DNA methylation.
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| Academic Significance and Societal Importance of the Research Achievements |
健康長寿獲得のためには、要支援の最大要因であるサルコペニアなどの運動機能退行メカニズムの理解とその予防・治療法の開発が必須である。そのために遺伝的要因の同定と、老化などの環境因子を含めた後天的要因の理解が必要である。本研究では、後天的要因のエフェクターと考えられるエピゲノム制御として、DNAの維持メチル化が骨格筋の恒常性維持に必須であり、特に筋再生において重要な役割を果たしていることを見出した。
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Report
(4 results)
Research Products
(80 results)
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[Journal Article] Uhrf1 governs the proliferation and differentiation of muscle satellite cells.2022
Author(s)
Sakai H, Sawada Y, Tokunaga N, Tanaka K, Nakagawa S, Sakakibara I, Ono Y, Fukada SI, Ohkawa Y, Kikugawa T, Saika T, Imai Y.
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Journal Title
iScience.
Volume: 25
Issue: 3
Pages: 103928-103928
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] GPRC5A facilitates cell proliferation through cell cycle regulation and correlates with bone metastasis in prostate cancer2020
Author(s)
Sawada Y, Kikugawa T, Iio H, Sakakibara I, Yoshida S, Ikedo A, Yanagihara Y, Saeki N, Gyorffy B, Kishida T, Okubo Y, Nakamura Y, Miyagi Y, Saika T, Imai Y.
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Journal Title
International Journal of Cancer
Volume: 146
Issue: 5
Pages: 1369-1382
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Micro-CT imaging analysis for the effects of ibandronate and eldecalcitol on secondary osteoporosis and arthritis in adjuvant-induced arthritis rats2019
Author(s)
Ono Y, Miyakoshi N, Kasukawa Y, Imai Y, Nagasawa H, Tsuchie H, Akagawa M, Nagahata I, Yuasa Y, Sato C, Kawatani M, Shimada Y.
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Journal Title
Biomedical Research
Volume: 40
Issue: 5
Pages: 197-205
DOI
NAID
ISSN
0388-6107, 1880-313X
Year and Date
2019-10-01
Related Report
Peer Reviewed
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[Journal Article] Fibroblast Growth Factor 9 Is Upregulated Upon Intervertebral Mechanical Stress-Induced Ligamentum Flavum Hypertrophy in a Rabbit Model.2019
Author(s)
Hayashi K, Suzuki A, Terai H, Ahmadi SA, Rahmani MS, Hasib MM, Habibi H, Hori Y, Yamada K, Hoshino M, Toyoda H, Takahashi S, Tamai K, Ohyama S, Imai Y, Nakamura H.
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Journal Title
Spine.
Volume: 44(20)
Issue: 20
Pages: E1172-E1180
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Uhrf1 governs the proliferation and differentiation of muscle satellite cells2021
Author(s)
Hiroshi Sakai, Yuichiro Sawada, Naohito Tokunaga, Kaori Tanaka, So Nakagawa, Iori Sakakibara, Yusuke Ono, So-ichiro Fukada, Yasuyuki Ohkawa, Tadahiko Kikugawa, Takashi Saika, Yuuki Imai
Organizer
第7回日本筋学会学術集会
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[Presentation] Yuuki Imai2019
Author(s)
The role of an epigenetic regulator, Uhrf1, in musculoskeletal biology
Organizer
29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019
Related Report
Int'l Joint Research / Invited
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