• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of novel drugs for CKD

Research Project

Project/Area Number 26293031
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionTohoku University

Principal Investigator

ABE Takaaki  東北大学, 医工学研究科, 教授 (80292209)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Keywordsトランスポーター / SLCO4C1 / 尿毒素 / 腎不全 / インドール / 有機アニオントランスポーター / メタボローム
Outline of Final Research Achievements

The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. Recently, we have revealed that human kidney-specific organic anion transporter SLCO4C1 excretes uremic toxins, and the up-regulation of SLCO4C1 resulted in the reduction of blood pressure and renal inflammation in a CKD. We revealed that the uremic toxin transporter, SLCO4C1, is negatively regulated by a representative uremic toxin indoxyl sulfate, through a transcription factor GATA3. The removal of indoxyl sulfate and blocking its signaling pathway should be an effective strategy to restore the SLCO4C1-mediated renal excretion of uremic toxins.
In addition, among uremic toxins, indole-3-acetic acid significantly increased the cellular ATP level in Hep3B human cells. Indole derivatives may represent a novel therapeutic strategy for treating AKI and CKD as a mitochondria-homing drug.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (17 results)

All 2017 2016 2015 2014

All Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 6 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Evaluation of the impact of gut microbiota on uremic solute accumulation by a Capillary Electrophoresis-Time Of Flight Mass Spectroscopy-based metabolomics approach.2017

    • Author(s)
      2.Mishima E., Fukuda, Mukawa C, Yuri A, Kanemitsu Y., Matsumoto Y., Akiyama Y., Fukuda N. , Tsukamoto H., Asaji K., Shima H., Kikuchi K., Suzuki C., Suzuki T., Tomioka Y., Soga T., Ito S. and Takaaki Abe T.
    • Journal Title

      Kidney International

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mitochonic acid 5 binds mitochondria and ameliorates renal tubular and cardiac myocyte damage2016

    • Author(s)
      Suzuki T, Kanno SI, Abe T. et al
    • Journal Title

      J Am Soc Nephrol.

      Volume: 27 Issue: 7 Pages: 1925

    • DOI

      10.1681/asn.2015060623

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Interactions of crizotinib and gefitinib with organic anion-transporting polypeptides (OATP)1B1, OATP1B3, and OATP2B1: gefitinib shows contradictory interaction with OATP1B3.2016

    • Author(s)
      Sato T., Ito H., Hirata A., Abe T., Mano N. and Yamaguchi H.
    • Journal Title

      Xenobiotica

      Volume: 12 Issue: 1 Pages: 1-6

    • DOI

      10.1080/00498254.2016.1275880

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mitochonic Acid 5 (MA-5), a Derivative of the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases2015

    • Author(s)
      Suzuki T, Yamaguchi H, Kikusato M, Matsuhashi T, Matsuo A, Sato T, Oba Y, Watanabe S, Minaki D, Saigusa D, Shimbo H, Mori N, Mishima E, Shima H, Akiyama Y, Takeuchi Y, Yuri A, Kikuchi K, Toyohara T, Suzuki C, Kohzuki M, Anzai J, Mano N, Kure S, Yanagisawa T, Tomioka Y, Toyomizu M, Ito S, Osaka H, Hayashi K, Abe T
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 236 Issue: 3 Pages: 225-232

    • DOI

      10.1620/tjem.236.225

    • NAID

      130005083526

    • ISSN
      0040-8727, 1349-3329
    • URL

      https://pure.teikyo.jp/en/publications/f34848a7-3f52-481e-850d-fae28c8f317e

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage2015

    • Author(s)
      Suzuki T
    • Journal Title

      J Am Soc Nephrol.

      Volume: 11 Pages: 1-8

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Exonic Mutations in the SLC12A3 Gene Cause Exon Skipping and Premature Termination in Gitelman Syndrome2015

    • Author(s)
      竹内陽一、三島英換、他12名
    • Journal Title

      J Am Soc Nephrol

      Volume: 26 Issue: 2 Pages: 271-279

    • DOI

      10.1681/asn.2013091013

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative Targeted Absolute Proteomics for 28 Transporters in Brush-Border and Basolateral Membrane Fractions of Rat Kidney.2015

    • Author(s)
      Uchida Y
    • Journal Title

      J Pharm Sci

      Volume: 105 Issue: 2 Pages: 1011-16

    • DOI

      10.1002/jps.24645

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD.2015

    • Author(s)
      Mishima E.
    • Journal Title

      J Am Soc Nephrol.

      Volume: 26 Pages: 271-279

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD2014

    • Author(s)
      Eikan Mishima, Shinji Fukuda, Hisato Shima, Akiyoshi Hirayama, Yasutoshi Akiyama, Yoichi Takeuchi, Noriko N Fukuda, Takehiro Suzuki, Chitose Suzuki, Akinori Yuri, Koichi Kikuchi, Yoshihisa Tomioka, Sadayoshi Ito, Tomoyoshi Soga, and Takaaki Abe
    • Journal Title

      J Am Soc Nephrol

      Volume: 26 Issue: 8 Pages: 1-8

    • DOI

      10.1681/asn.2014060530

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Organic anion transporting polypeptides 1B1 and 1B3 play an important role in uremic toxin handling and drug-uremic toxin interactions in the liver.2014

    • Author(s)
      Sato T.
    • Journal Title

      J Pharm Pharm Sci.

      Volume: 17 Pages: 475-484

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Kidney and Uremic Toxin Removal: Glomerulus or Tubule?2014

    • Author(s)
      Masereeuw R
    • Journal Title

      Semin Nephrol.

      Volume: 34 Issue: 2 Pages: 191-208

    • DOI

      10.1016/j.semnephrol.2014.02.010

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Proteomics and Metabolomics as Tools to Unravel Novel Culprits and Mechanisms of Uremic Toxicity: Instrument or Hype?2014

    • Author(s)
      Mullen W.
    • Journal Title

      Semin Nephrol.

      Volume: 34 Issue: 2 Pages: 180

    • DOI

      10.1016/j.semnephrol.2014.02.009

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] 慢性腎臓病(CKD)と腸内細菌叢2017

    • Author(s)
      阿部高明
    • Organizer
      第20回日本病態栄養学会年次学術集会
    • Place of Presentation
      京都・京都国際会議場
    • Year and Date
      2017-01-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Development of a novel mitochondrial drug, MA-52016

    • Author(s)
      阿部高明
    • Organizer
      The 13th Conference of Asian Society for Mitochondrial Research and Medicine
    • Place of Presentation
      東京・TKPガーデンシティ品川
    • Year and Date
      2016-10-31
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腸内細菌叢と腎疾患2016

    • Author(s)
      阿部高明
    • Organizer
      第46回腎臓学会西部学術大会
    • Place of Presentation
      宮崎・シーガイアコンベンションセンター
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 尿毒素によるエピジェネティック修飾と腎不全2016

    • Author(s)
      阿部高明
    • Organizer
      第61回透析医学会
    • Place of Presentation
      大阪・大阪国際会議場
    • Year and Date
      2016-06-11
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] エリスロポエチン産生増強化合物の作用機序の解明2014

    • Author(s)
      大庭悠貴
    • Organizer
      第57回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-07-06
    • Related Report
      2014 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2018-12-17  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi