New strategy for overcoming Pi toxicity by modulating the function of inorganic phosphate (Pi) network.
| Project/Area Number |
17H04190
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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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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MIYAMOTO Kenichi 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (70174208)
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| Co-Investigator(Kenkyū-buntansha) |
金子 一郎 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (40389515)
永森 收志 奈良県立医科大学, 医学部, 教授 (90467572)
辰巳 佐和子 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (80420545)
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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 |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | リン / リン輸送体 / FGF23 / klotho / ノックアウトマウス / 慢性腎臓病 / 骨細胞 / トランスポーター / 遺伝子欠損マウス / 尿細管 |
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| Outline of Final Research Achievements |
Inorganic phosphate (Pi) homeostasis plays a very important role in the progression of chronic kidney disease (CKD) and the prognosis of dialysis patients. Abnormal Pi metabolism arises from early CKD, and maintenance of Pi balance is essential for the prevention of cardiovascular disease. In recent years, Pi network (Pnet) including the fibroblast-like growth factor FGF23 / klotho system controls Pi transport and its toxicity. Pnet contains Psome, a complex as a target molecule of the FGF23 / klotho system. In this study, we investigated the role of TMD2 as a constituent molecule of Psome. TMD2KO mice showed abnormal Pi metabolism, suggesting that they may be involved in FGF23 / klotho signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
CKD（慢性腎臓病）患者数は、 1300万人といわれて、また高齢者になるほどCKDが多くなる。高血圧、糖尿病、脂質代謝異常、肥満やメタボリックシンドローム、などは CKD悪化の原因となる。さらにCKDは、心筋梗塞や脳卒中といった心血管疾患の重大な危険因子になっています。リン代謝は、心血管疾患進展の重要な原因の一つに考えられており、その解明は重要である。本研究では、リン代謝の中核となる Psomeの構成因子を明らかにして、その病態への関与を検討したものである。
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Report
(4 results)
Research Products
(85 results)
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[Journal Article] Role of sodium-dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages.2020
Author(s)
Hanazaki A, Ikuta K, Sasaki S, Sasaki S, Koike M, Tanifuji K, Arima Y, Kaneko I, Shiozaki Y, Tatsumi S, Hasegawa T, Amizuka N, Miyamoto KI, Segawa H.
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Journal Title
Physiological Reports
Volume: Feb;8(3)
Pages: 1-16
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Analysis of opossum kidney NaPi-IIc sodium-dependent phosphate transporter to understand Pi handling in human kidney.2019
Author(s)
Fujii T, Shiozaki Y, Segawa H, Nishiguchi S, Hanazaki A, Noguchi M, Kirino R, Sasaki S, Tanifuji K, Koike M, Yokoyama M, Arima Y, Kaneko I, Tatsumi S, Ito M, Miyamoto KI.
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Journal Title
Clin Exp Nephrol.
Volume: 23(3)
Pages: 313-324
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Eldecalcitol Causes FGF23 Resistance for Pi Reabsorption and Improves Rachitic Bone Phenotypes in the Male Hyp Mouse.2018
Author(s)
Kaneko I, Segawa H, Ikuta K, Hanazaki A, Fujii T, Tatsumi S, Kido S, Hasegawa T, Amizuka N, Saito H, Miyamoto KI.
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Journal Title
Endocrinology.
Volume: 159(7)
Pages: 2741-2758
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling2018
Author(s)
Ikuta K, Segawa H, Sasaki S, Hanazaki A, Fujii T, Kushi A, Kawabata Y, Kirino R, Sasaki S, Noguchi M, Kaneko I, Tatsumi S, Ueda O, Wada NA, Tateishi H, Kakefuda M, Kawase Y, Ohtomo S, Ichida Y, Maeda A, Jishage KI, Horiba N, Miyamoto KI.
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Journal Title
Clinical and Experimental Nephrology
Volume: 印刷中
Pages: 1497-1503
DOI
Related Report
Peer Reviewed
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[Journal Article] The sodium phosphate cotransporter family and nicotinamide phosphoribosyltransferase contribute to the daily oscillation of the plasma inorganic phosphate concentration.2018
Author(s)
Miyagawa A, Tatsumi S, Takahama W, Fujii O, Nagamoto K, Kinoshita E, Nomura K, Ikuta K, Fujii T, Hanazaki A, Kaneko I, Segawa H, Miyamoto KI.
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Journal Title
Kidney International
Volume: 印刷中
Pages: 1073-1085
DOI
Related Report
Peer Reviewed
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[Journal Article] Effect of Osteocyte-Ablation on Inorganic Phosphate Metabolism: Analysis of Bone-Kidney-Gut Axis2018
Author(s)
Fujii O, Tatsumi S, Ogata M, Arakaki T, Sakaguchi H, Nomura K, Miyagawa A, Ikuta K, Hanazaki A, Kaneko I, Segawa H, Miyamoto KI.
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Journal Title
Front Endocrinol (Lausanne).
Volume: 8
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex2018
Author(s)
Liang Weng , Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical Significance and Phenotype of MTA1 Expression in Esophageal Squamous Cell Carcinoma.2017
Author(s)
Honjo H, Toh Y, Sohda M, Suzuki S, Kaira K, Kanai Y, Nagamori S, Oyama T, Yokobori T, Miyazaki T, Kuwano H.
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Journal Title
Anticancer Res.
Volume: 37(8)
Pages: 4147-4155
Related Report
Peer Reviewed / Open Access
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[Journal Article] Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells.2017
Author(s)
Ikeda K, Kinoshita M, Kayama H, Nagamori S, Kongpracha P, Umemoto E, Okumura R, Kurakawa T, Murakami M, Mikami N, Shintani Y, Ueno S, Andou A, Ito M, Tsumura H, Yasutomo K, Ozono K, Takashima S, Sakaguchi S, Kanai Y, Takeda K.
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Journal Title
Cell reports
Volume: 21
Pages: 1824-1838
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] PiT-2 Is the Main Transporter Responsible for Intestinal Phosphate Absorption in Human.2019
Author(s)
Yasuhiro Ichida, Daniel Weis, Shuichi Ohtomo, Nadine Kaesler, Christoph Kuppe, Tessai Yamamoto, Naoaki Murao, Hiroko Segawa, Yoshiki Kawabe, Naoshi Horiba, Ken-ichi Miyamoto, Jurgen Floege.
Organizer
American Society of Nephrology kidney week2019.
Related Report
Int'l Joint Research
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