Functional analysis of R3h domain containing-like, a novel skeletal satellite-cell-expressed gene, for investigating new treatment strategy of sarcopenia
Project/Area Number |
16K09229
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General internal medicine(including psychosomatic medicine)
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Research Institution | Chiba University |
Principal Investigator |
Takemoto Minoru 千葉大学, 大学院医学研究院, 特任教授 (60447307)
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Co-Investigator(Kenkyū-buntansha) |
石川 崇広 千葉大学, 医学部附属病院, 特任助教 (00749426)
横手 幸太郎 千葉大学, 大学院医学研究院, 教授 (20312944)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 骨格筋 / サルコペニア / 筋衛生細胞 / 老年医学 |
Outline of Final Research Achievements |
In this study, we identified a novel skeletal satellite-cell-expressed gene, R3h domain containing-like (R3hdml). R3hdml protein was secreted from cultured myotubes into the conditioned media, suggesting that R3hdml a novel myokine. In R3hdml knock out (KO) mice, the body weight and skeletal muscle mass were lower than that in the wild type control mice. Expression levels of cell cycle-related markers within the skeletal muscle was decreased in R3hdml KO mice compared with control mice. Cardiotoxin (CTX) was injected into the skeletal muscle to induce skeletal muscle regeneration after injury; consequently, the expression of R3hdml increased during skeletal muscle regeneration. Recovery of hand grip strength after CTX injection was significantly impaired in the R3hdml KO mice and overexpression of R3hdml rescued this decreased hand grip strength. Our results indicate that R3hdml is important for skeletal muscle development as well as regeneration.
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Academic Significance and Societal Importance of the Research Achievements |
高齢化社会を迎えている今、健康長寿を達成するためにもサルコペニアなどの骨格筋関連疾患のメカニズムの解明と治療法の確立は急務である。骨格筋は優れた再生能力をもち、障害を受けても速やかに機能を回復する。この再生には筋衛星細胞が重要な役割をはたしている。本研究はR3hdml という新しい筋衛星細胞発現遺伝子を中心にした研究であり新しい切り口でサルコペニア発症機序の解明やさらには治療応用に繋がることが期待される。
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development2018
Author(s)
Ide S, Finer G, Maezawa Y, Onay T, Souma T, Scott R, Ide K, Akimoto Y, Li C,Ye M, Zhao X, Baba Y, Minamizuka T, Jin J, Takemoto M, Yokote K, Quaggin SE
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Journal Title
J Am Soc Nephrol
Volume: 29
Issue: 12
Pages: 2795-2808
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Biallelic WRN Mutations in Newly Identified Japanese Werner Syndrome Patients2018
Author(s)
Maezawa Y, Kato H, Takemoto M, Watanabe A, Koshizaka M, Ishikawa T, Sargolzaeiaval F, Kuzuya M, Wakabayashi H, Kusaka T, Yokote K, Oshima J
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Journal Title
Mol Syndromol
Volume: 9
Issue: 4
Pages: 214-218
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Immune-mediated acquired lecithin-cholesterol acyltransferase deficiency: A case report and literature review2018
Author(s)
Ishibashi R, Takemoto M, Tsurutani Y, Kuroda M, Ogawa M, Wakabayashi H, Uesugi N, Nagata M, Imai N, Hattori A, Sakamoto K, Kitamoto T, Maezawa Y, Narita I, Hiroi S, Furuta A, Miida T, Yokote K
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Journal Title
J Clin Lipidol
Volume: 12
Issue: 4
Pages: 888-897
DOI
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Peer Reviewed
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[Journal Article] Altered cerebral blood flow in the anterior cingulate cortex is associated with neuropathic pain.2018
Author(s)
Watanabe K, Hirano S, Kojima K, Nagashima K, Mukai H, Sato T, Takemoto M, Matsumoto K, Iimori T, Isose S, Omori S, Shibuya K, Sekiguchi Y, Beppu M, Amino H, Suichi T, Yokote K, Uno T, Kuwabara S, Misawa S.
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Journal Title
Journal of Neurology Neurosurgry Psychiatry
Volume: 印刷中
Issue: 10
Pages: 1082-1087
DOI
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Peer Reviewed
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[Journal Article] Physician-initiated clinical study of limb ulcers treated with a functional peptide, SR-0379: from discovery to a randomized, double-blind, placebo-controlled trial2018
Author(s)
Nakagami H, Sugimoto K, Ishikawa T, Fujimoto T, Yamaoka T, Hayashi M, Kiyohara E, Ando H, Terabe Y, Takami Y, Yamamoto K, Takeya Y, Takemoto M, Koshizaka M, Ebihara T, Nakamura A, Nishikawa M, Yao XJ, Hanaoka H, Katayama I, Yokote K, Rakugi H
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Journal Title
NPJ Aging Mech Dis
Volume: 4
Issue: 1
Pages: 2-2
DOI
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Peer Reviewed / Open Access
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[Journal Article] Association of serum levels of antibodies against MMP1, CBX1, and CBX5 with transient ischemic attack and cerebral infarction2017
Author(s)
Wang H,Zhang X-M,Tomiyoshi G,Nakamura R,Shinmen N,Kuroda H,Kimura R,Mine S,Kamitsukasa I,Wada T,Aotsuka A,Yoshida Y,Kobayashi E,Matsutani T,Iwadate Y,Sugimoto K,Mori M,Uzawa A,Muto M,Kuwabara S,Takemoto M,Kobayashi K,Kawamura H,Ishibashi R,Yokote K,Ohno M,
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Journal Title
Oncotarget
Volume: 9
Issue: 5
Pages: 5600-5613
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Outcomes of laparoscopic sleeve gastrectomy in elderly obese Japanese patients.2017
Author(s)
Hayashi A, Maeda Y, Takemoto M, Tokuyama H, Koide H, Kitahara A, Hayashi H, Kitamoto T, Yamaga M, Kobayashi K, Yokote K.
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Journal Title
Geriatr Gerontol Int.
Volume: -
Issue: 11
Pages: 2068-2073
DOI
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Peer Reviewed / Open Access
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[Journal Article] WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects.2017
Author(s)
Yokote K, Chanprasert S, Lee L, Eirich K, Takemoto M, Watanabe A, Koizumi N, Lessel D, Mori T, Hisama FM, Ladd PD, Angle B, Baris H, Cefle K, Palanduz S, Ozturk S, Chateau A, Deguchi K, Easwar TK, Federico A, Fox A, Grebe TA, Hay B, Nampoothiri S, Seiter K, Streeten E, Poke G, Poot M, Posmyk R, Oshima J
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Journal Title
Hum Mutat
Volume: 38
Issue: 1
Pages: 7-15
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Combination of cilostazol and probucol protected podocytes from lipopolysaccharide-induced injury by both anti-inflammatory and anti-oxidative mechanisms.2016
Author(s)
He P, Kawamura H, Takemoto M, Maezawa Y, Ishikawa T, Ishibashi R, Sakamoto K, Shoji M, Hattori A, Yamaga M, Ide S, Ide K, Hayashi A, Tokuyama H, Kobayashi K, Yokote K.
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Journal Title
J Nephrol.
Volume: -
Issue: 4
Pages: 531-541
DOI
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Peer Reviewed / Open Access
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[Journal Article] Matricellular protein CCN3 mitigates abdominal aortic aneurysm.2016
Author(s)
Zhang C, van der Voort D, Shi H, Zhang R, Qing Y, Hiraoka S, Takemoto M, Yokote K, Moxon JV, Norman P, Kuivaniemi H, Atkins GB, Gerson SL, Shi GP, Golledge J, Dong N, Perbal B, Prosdocimo DA, Lin Z
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Journal Title
J Clin Invest
Volume: 126
Issue: 4
Pages: 1282-1299
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Peer Reviewed / Open Access
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[Journal Article] A novel podocyte gene, Semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation.2016
Author(s)
Ishibashi R, Takemoto M, Akimoto Y, Ishikawa T, He P, Maezawa Y, Sakamoto K, Tsurutani Y, Ide S, Ide K, Kawamura H, Kobayashi K, Tokuyama H, Tryggvason K, Betsholtz C, Yokote K
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Journal Title
Scientific Report
Volume: 6
Issue: 1
Pages: 25955-25955
DOI
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Peer Reviewed / Open Access
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[Presentation] Comparison of ipragliflozin and metformin for visceral fat reduction in elderly patients with type 2 diabetes: a prospective, blinded-endpoint, randomized controlled study2018
Author(s)
Koshizaka M, Ishikawa K, Ishibashi R, Yokoh H, Sakamoto K, Ishikawa T, Maezawa Y, Takemoto M, Yokote K, PRIME-V Study Group
Organizer
54th EASD
Related Report
Int'l Joint Research
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[Presentation] R3h domain containing-like (R3hdml) has pivotal roles in skeletal muscle development and regeneration2017
Author(s)
Sakamoto K, Takemoto M, Furuichi Y, Takahashi M, Akimoto Y, Yamamoto M, Ishikawa T, Shimizu T, Manabe Y, Fujii N, Maezawa Y, Betsholtz C, Yokote K.
Organizer
American Diabetes Association (ADA) 77th Scientific Sessions
Related Report
Int'l Joint Research
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[Presentation] R3h domain containing-like (R3hdml) has crucial roles in skeletal muscle development and regeneration through the regulation of satellite cell proliferation.2017
Author(s)
Sakamoto K, Takemoto M, Furuichi Y, Takahashi M, Akimoto Y, Yamamoto M, Ishikawa T, Shimizu T, Manabe Y, Fujii N, Maezawa Y, Yokote K.
Organizer
Keystone Symposia - Aging and Mechanisms of Aging-Related Disease.
Related Report
Int'l Joint Research
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