Kidney transporter and gut microbiota as therapeutic targets for chronic kidney disease

• Project/Area Number: 26860094
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Tohoku University
• Principal Investigator: Akiyama Yasutoshi 東北大学, 医学系研究科, 非常勤講師 (70635557)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 尿毒素 / 腸内細菌 / ミトコンドリア / tRNA / MA-5 / 慢性腎不全 / 血液透析 / 腸内細菌叢

Outline of Final Research Achievements

(1) We comprehensively evaluated serum concentrations of 122 ionic compounds in hemodialysis (HD) patients. We identified 38 solutes and 23 solutes that were higher and lower, respectively, in HD patients than non-dialyzed chronic kidney disease (CKD) patients. (2) We revealed that a newly synthesized indole derivative (MA-5) increased cellular ATP level and survival of fibroblasts from patients with mitochondrial diseases. These data suggest that MA-5 has the potential to become a novel therapeutic drug for treatment of mitochondrial diseases. (3) We revealed that ClC-2 chloride channel activator lubiprostone improved the gut microbiota, resulting in amelioration of CKD progression. (4) Using next-generation sequencing, we examined whether ribonuclease angiogenin (ANG) cleaves CCA-termini of tRNAs in vivo. The proportion of tRNA-derived fragments with CCA did not increase in ANG-treated cells, suggesting that ANG does not cleave CCA-termini in vivo.

Research Products

• [Journal Article] RNA biology of angiogenin: Current state and perspectives (2017)
  • Author(s): Shawn M Lyons, Marta M Fay, Yasutoshi Akiyama, Paul J Anderson, and Pavel Ivanov
  • Journal Title: RNA Biology Volume: 14 Issue: 2 Pages: 171-178
  • DOI: 10.1080/15476286.2016.1272746
  • Peer Reviewed
• [Journal Article] Mitochonic acid 5 binds mitochondria and ameliorates renal tubular and cardiac myocyte damage (2016)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [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 Diseases. (2015)
  • Author(s): T Suzuki, H Yamaguchi, M Kikusato, （他11名）, Y Akiyama, Y Takeuchi, A Yuri, K Kikuchi, T Toyohara, C Suzuki, M Kohzuki, J Anzai, N Mano, S Kure, T Yanagisawa, Y Tomioka, M Toyomizu, S Ito, H Osaka, K Hayashi, and T Abe
  • Journal Title: Tohoku J Exp Med Volume: 236 Pages: 225-232
  • NAID: 130005083526
  • Peer Reviewed
• [Journal Article] Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD (2014)
  • 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
  • Peer Reviewed
• [Presentation] CE-MSによる透析患者に特異的な尿毒素の網羅的探索 (2015)
  • Author(s): 秋山泰利
  • Organizer: 日本透析医学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-06-26 – 2015-06-28
• [Presentation] CE-MSによる透析患者に特異的な尿毒素の網羅的探索 (2015)
  • Author(s): 秋山泰利
  • Organizer: 日本透析医学会総会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2015-06-26