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Study on the FGF23 metabolic regulation mechanism derived bone as a novel phosphaturic factor in renal insufficient status.

Research Project

Project/Area Number 16K09652
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionWakayama Medical University

Principal Investigator

Shigematsu Takashi  和歌山県立医科大学, 医学部, 教授 (30187348)

Co-Investigator(Kenkyū-buntansha) 大矢 昌樹  和歌山県立医科大学, 医学部, 講師 (90550301)
Project Period (FY) 2016-10-21 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
KeywordsFGF23 / 骨細胞 / 骨芽細胞 / ビタミンD / リン / FGF 23 / 活性型ビタミンD / 活性型ビタミンD受容体 / 線維芽細胞増殖因子23 / 高リン血症 / 骨組織 / 腎機能障害 / 骨細胞 Osteocyte / Klotho / 慢性腎臓病 (CKD) / 活性型Vitamin D / リン代謝 / 腎障害
Outline of Final Research Achievements

We estimated the FGF23 production in vitro among isolated osteoblasts, osteocytes and osteoclast in bone constitution cells without osteocyte harvest. The osteoblastic Cell Line MC3T3-E1 cells have ability to be calcified spontaneously. We changed these cells into osteocytes by ascorbic acid and phosphate overload in vitro. We estimate the FGF23 mRNA expression at each stage from osteoblast to osteocyte. The both of matured osteoblast and immature osteocyte had the most effective production ability. We discovered that the most powerful stimulator on FGF23 is active vitamin D and analogues (vitamin D receptor activator), but not phosphate loading.
In addition, we were able to observe the even plasmatoid dendritic cell in spleen and calcified vessel as an ectopic calcification have also FGF23 production ability. These phenomena might explain the effect of FGF23 on cardiovascular events and immune system. This area is needed further investigation.

Academic Significance and Societal Importance of the Research Achievements

FGF23は腎機能障害者においては、生命予後と密接に関係することが明らかとなりつつある。またFGF23受容体となるKlotho蛋白をコードするKlotho遺伝子は長寿遺伝子すなわち抗老化作用を有することが明らかとなった。
本研究成果は、この老化の本質的なメカニズムの一端を明らかにするものであり、今後の抗老化作用を有する創薬にもつながる成果である。さらには心血管病の進展や免疫系への作用など広い分野の研究領域を啓く可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] Effects of the intravenous calcimimetic etelcalcetide on bone turnover and serum fibroblast growth factor 23: post-hoc analysis of an open-label study.2018

    • Author(s)
      Takashi Shigematsu, Masafumi Fukagawa, Keitaro Yokoyama, Takashi Akiba, Akifumi Fujii, Motoi Odani, Tadao Akizawa
    • Journal Title

      Clinical Therapeutics

      Volume: 40 Issue: 12 Pages: 2099-2111

    • DOI

      10.1016/j.clinthera.2018.10.016

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intravenous maxacalcitol therapy correlates with serum fibroblast growth factor 23 levels in hemodialysis patients independent of serum phosphate or calcium levels2018

    • Author(s)
      Masaki Ohya,* Mitsuru Yashiro, Tomohiro Sonou, Kouji Okuda, Toru Mima, Yoshinori Tone, Shigeo Negi, Yasushi Saika, Takashi Shigematsu
    • Journal Title

      Contrib Nephrol.

      Volume: 196 Pages: 44-51

    • DOI

      10.1159/000485696

    • ISBN
      9783318062977, 9783318062984
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dietary changes involving Bifidobacterium longum and other nutrients delays CKD progression.2018

    • Author(s)
      Yuko Iwashita, Masaki Ohya (Corresponding Author), Mitsuru Yashiro, Tomohiro Sonou, Kazuki Kawakami, Yuri Nakashima, Takuro Yano, Yu Iwashita, Toru Mima, Shigeo Negi,
    • Journal Title

      Am J Nephrol

      Volume: 47 Issue: 5 Pages: 325-332

    • DOI

      10.1159/000488947

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FGF23 modulates the effects of erythropoietin on gene expression in renal epithelial cells2018

    • Author(s)
      Yashiro Mitsuru、Ohya Masaki、Mima Toru、Ueda Yumi、Nakashima Yuri、Kawakami Kazuki、Ishizawa Yohei、Yamamoto Shuto、Kobayashi Sou、Yano Takurou、Tanaka Yusuke、Okuda Kouji、Sonou Tomohiro、Shoshihara Tomohiro、Iwashita Yuko、Iwashita Yu、Tatsuta Kouichi、Matoba Ryo、Negi Shigeo、Shigematsu Takashi
    • Journal Title

      International Journal of Nephrology and Renovascular Disease

      Volume: Volume 11 Pages: 125-136

    • DOI

      10.2147/ijnrd.s158422

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intravenous maxacalcitol therapy correlates with serum fibroblast growth factor 23 levels in hemodialysis patients independent of serum phosphate or calcium levels2018

    • Author(s)
      Masaki Ohya,1* Mitsuru Yashiro,1 Tomohiro Sonou,1 Kouji Okuda,1 Toru Mima, Yoshinori Tone, Shigeo Negi, Yasushi Saika, Takashi Shigematsu
    • Journal Title

      Contribution to Nephrology

      Volume: 194

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Possible prevention of uremic nausea by vitamin D receptor activators in non-dialysis patients with stage 5 chronic kidney disease2017

    • Author(s)
      Ikeda M, Ueda Y, Maruyama Y, Yokoyama K, Yokoo T, Joki N, Ando R, Shinoda T, Inaguma D, Yamaka T, Komatsu Y, Koiwa F, Sakaguchi T, Negi S, Shigematsu T
    • Journal Title

      Clin Exp Nephrol. 2016 Nov 14. [Epub ahead of print]

      Volume: 21 Issue: 5 Pages: 825-834

    • DOI

      10.1007/s10157-016-1355-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression and localization of Fibroblast Growth Factor (FGF) 23 and Klotho in the spleen: Its physiological and functional implications.2016

    • Author(s)
      Yuri Nakashima, Toru Mima, Mitsuru Yashiro, Tomohiro Sonou, Masaki
    • Journal Title

      Growth Factors

      Volume: 印刷中 Issue: 5-6 Pages: 195-202

    • DOI

      10.1080/08977194.2016.1273222

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] FGF23-Klotho axis involving B cell immune response and possibly causing for ESRD patients as immunocompromised hosts.2018

    • Author(s)
      Toru Mima, Yuri Nakashima, Masaki Ohya, Mitsuru Yashiro, Kazuki Kawakami, Shigeo Negi, Takashi Shigematsu
    • Organizer
      ISN Frontiers Meetings 2018.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 1,25-Dihydroxyvitamin D   Stimulation Increases FGF23 Expression in Calcified Vessels Under High Phosphate Condition2018

    • Author(s)
      Masaki Ohya, Kazuki Kawakami, Tomohiro Sonou, Mitsuru Yashiro, Toru Mima, Shigeo Negi, Takashi Shigematsu.
    • Organizer
      ASN Kidney Week 2018.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Crosstalk between FGF23 and erythropoietin signaling in renal tubule epithelial cells.2018

    • Author(s)
      Mitsuru Yashiro, Toru Mima, Masaki Ohya, Yuri Nakashima, Shigeo Negi, Takashi Shigematsu
    • Organizer
      ISN Frontiers Meetings 2018.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] FGF23とビタミンD~石灰化血管におけるビタミンD 刺激によるFGF23産生~2018

    • Author(s)
      大矢昌樹・河上和紀・重松隆
    • Organizer
      第63回日本透析医学会学術集会・総会 ワークショップ
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] FGF23-Klotho axis involving B cell immune response and possibly causing for ESRD patients as immunocompromised hosts.2018

    • Author(s)
      Toru Mima, Yuri Nakashima, Masaki Ohya, Mitsuru Yashiro, Kazuki Kawakami, Shigeo Negi, Takashi Shigematsu
    • Organizer
      Int, Soc. Nephrology Frontiers Meeting 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] CKD-MBD up date 20162017

    • Author(s)
      重松隆、小岩文彦
    • Organizer
      第62回日本透析医学会学術集会・総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Calcimimetics2017

    • Author(s)
      重松隆
    • Organizer
      第62回日本透析医学会学術集会・総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Remarks] 和歌山県立医科大学 腎臓内科学講座

    • URL

      http://www.wakayama-med.ac.jp/dept/igakubu/160601/index.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-10-24   Modified: 2020-03-30  

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