Development of novel drugs for CKD
| Project/Area Number |
26293031
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
ABE Takaaki 東北大学, 医工学研究科, 教授 (80292209)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(17 results)
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[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.
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Journal Title
Kidney International
Volume: 印刷中
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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
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Journal Title
The Tohoku Journal of Experimental Medicine
Volume: 236
Issue: 3
Pages: 225-232
DOI
NAID
ISSN
0040-8727, 1349-3329
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD.2015
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
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Journal Title
J Am Soc Nephrol.
Volume: 26
Pages: 1-8
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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
Invited
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