Elucidation of set-point mechanism for phosphate homeostasis and development of a novel therapeutic target for age-related diseases
| Project/Area Number |
19H04053
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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 59040:Nutrition science and health science-related
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TAKETANI Yutaka 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (30263825)
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| Co-Investigator(Kenkyū-buntansha) |
増田 真志 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (50754488)
山本 浩範 仁愛大学, 人間生活学部, 教授 (60314861)
大西 康太 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (80723816)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 高リン血症 / 異所性石灰化 / 慢性腎臓病 / 老化 / アルカリホスファターゼ / リン / 動脈硬化 / 小児 / リン感知機構 / リン代謝 / ビタミンＤ / 遺伝子多型 / エンハンサー / ビタミンD |
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| Outline of Research at the Start |
ヒトでもマウスでも、乳幼児期は骨の形成を促すためにカルシウムとともに骨の成分となるリンを必要とする目的で血中リン濃度が高くなっている。この時の血中リン濃度は、成人では慢性腎臓病患者などで見られるような血管石灰化を引き起こす濃度に匹敵するにも関わらず、通常は、乳幼児期に血管石灰化などの異常は生じない。乳幼児期と成熟期を比較することで、乳幼児期に血清リンを高値に保つメカニズムと石灰化を防止するメカニズムを解明することができれば、異所性石灰化や高リン血症の予防・治療において新たな治療法開発に応用することが期待できる。
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| Outline of Final Research Achievements |
Blood phosphorus concentration is maintained within a certain range by phosphate regulating hormones. The phosphorus concentration is high in infancy, then decreases as the child grows. The purpose of this study was to identify the factors that determine the phosphorus concentration and to clarify the mechanism of ectopic calcification suppression during the growth period. As a result, we found tissue-non-specific alkaline phosphatase in the liver as a new regulator that determines phosphorus concentration. In addition, an attempt to identify ectopic calcification inhibitor during the growth phase revealed that serum fetuin-A and vascular tissue-nonspecific alkaline phosphatase are important factors for the suppression of ectopic calcification during the growth phase.
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| Academic Significance and Societal Importance of the Research Achievements |
血中リン濃度は、乳幼児期には成人の２倍程度高く、成長するに従って低下する。この乳幼児期のリン濃度は、成人であれば高リン血症とされ、血管などに異所性石灰化を引き起こすには十分な濃度であるにもかかわらず、乳幼児期にはそのような異所性石灰化は生じない。異所性石灰化は老化関連病変の１つであり、慢性腎臓病や糖尿病などの多くの生活習慣病においてみられ、動脈硬化などを引き起こし、生命予後を規定する重要な因子である。本研究成果は、老化様病変である異所性石灰化の新たな予防法・治療法を開発するための基礎的成果である。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) induces ectopic calcification2022
Author(s)
Yimamu Y, Ohtani A, Takei Y, Furuichi A, Kamei Y, Yamanaka-Okumura H, Ohminami H, Masuda M, Miyazaki M, Yamamoto H, Taketani Y
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Journal Title
Journal of Clinical Biochemistry and Nutrition
Volume: 71
Issue: 2
Pages: 103-111
DOI
ISSN
0912-0009, 1880-5086
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Reduction of stearoyl-CoA desaturase (SCD) contributes muscle atrophy through the excess endoplasmic reticulum stress in chronic kidney disease.2020
Author(s)
Niida Y, Masuda M, Adachi Y, Yoshizawa A, Ohminami H, Mori Y, Ohnishi K, Yamanaka-Okumura H, Uchida T, Nikawa T, Yamamoto H, Miyazaki M, Taketani Y.
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Journal Title
J Clin Biochem Nutr.
Volume: 67(2)
Issue: 2
Pages: 179-187
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] All-trans retinoic acid reduces the transcriptional regulation of intestinal sodium-dependent phosphate co-transporter gene (Npt2b).2020
Author(s)
Masuda M, Yamamoto H, Takei Y, Nakahashi O, Adachi Y, Ohnishi K, Ohminami H, Yamanaka-Okumura H, Sakaue H, Miyazaki M, Takeda E, Taketani Y.
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Journal Title
The Biochemical journal.
Volume: 477(4)
Issue: 4
Pages: 817-831
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Dietary Phosphate Disturbs of Gut Microbiome in Mice2019
Author(s)
Naoko Oda, Kohei Sugihara, Miho Ikeda, Yuho Higashimura, Takashi Uebanso, Hirokazu Ohminami, Kohta Ohnishi, Masashi Masuda, Hisami Yamanaka-Okumura, Yutaka Taketani
Organizer
Kidney Week 2019, Annual Meeting of American Society of Nephrology
Related Report
Int'l Joint Research
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