mTORC1 as a therapeutic target for XLH
| Project/Area Number |
17K10092
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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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| Research Field |
Pediatrics
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| Research Institution | Osama Woman's and Children's Hospital |
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Principal Investigator |
Masanobu Kawai 地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 環境影響部門, 主任研究員 (50598117)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | リン / インスリン / PTEN / mTORC1 / FGF23 / phosphate / AKT / X連鎖性低リンくる病 / X連鎖性低リン性くる病 / 分枝鎖アミノ酸 |
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| Outline of Final Research Achievements |
Fibroblast growth factor 23 (FGF23) has been centric to the regulation of phosphate (Pi) metabolism; however, the regulatory network of FGF23 in osteocytes has not yet been defined in detail. In addition, accumulating evidence demonstrates the role for insulin signaling in the regulation of Fgf23 in bone. We herein investigated the role of PTEN (phosphatase and tensin homolog deleted from chromosome 10) in this regulation. We created mice lacking Pten expression mainly in osteocytes by crossing Pten-flox mice with Dmp1-Cre mice. The lack of Pten in the osteocytes of these mice was associated with decreased serum Fgf23 levels, which, in turn, resulted in reductions of urinary Pi excretion and elevations of serum Pi levels. Mechanistically, the insulin-induced suppression of Fgf23 expression was reversed in cells treated with the mTORC1 inhibitor, rapamycin.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、リン代謝制御機構が明らかとなってきており、インスリンシグナルによるFGF23制御機構が注目されている。臨床的には、インスリン抵抗性をきたすような肥満患者では、FGF23濃度が増加しており、肥満の病態形成におけるFGF23の役割が明らかになってきているが、その分子機序は不明であった。本研究成果は、インスリンによるFGF23制御機構の分子機序を明らかにしたものであり、骨細胞におけるインスリンシグナルが肥満症の病態形成に与える影響を理解する上で、重要な意味があると考えられる。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Policy Statement of Enteral Nutrition for Preterm and Very Low Birthweight Infants.2020
Author(s)
Mizuno K, Shimizu T, Shinobu Ida, Ito S, Inokuchi M, Ohura T,Okumura A, KawaiM,Kikuchi T, Sakurai M, Sugihara S, Suzuki M,Takitani K,Tanaka D,Mushiake S,Yoshiike N,Kodama H,Kazuo Okada K, Tsutsumi C, Hara M, Hanawa Y,Kawakami K, Inomata H, Oguni T,Bito Y,Uchida K, Akihide Sugiyama A.
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Journal Title
Pediatr Int.
Volume: 62
Issue: 2
Pages: 124-127
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] MIRAGE syndrome caused by a novel missense variant (p.Ala1479Ser) in the SAMD9 gene.2019
Author(s)
Onuma S, Wada T, Araki R, Wada K, Tanase-Nakao K, Narumi S, Fukui M, Shoji Y, Etani Y, Ida S, Kawai M.
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Journal Title
Hum Genome Var.
Volume: 7
Issue: 1
Pages: 4-4
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CYP7A1 expression in hepatocytes is retained with upregulated fibroblast growth factor 19 in pediatric biliary atresia.2019
Author(s)
Hasegawa Y, Kawai M, Bessho K, Yasuda K, Ueno T, Satomura Y, Konishi A, Kimura T, Ikeda K, Tachibana M, Miyoshi Y, Michigami T, Kondou H, Ozono K
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Journal Title
Hepatol Res
Volume: 49
Issue: 3
Pages: 314-323
DOI
Related Report
Peer Reviewed
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