Identification and clinical implication of biomarkers for mitochondrial diseases

• Project/Area Number: 18K15698
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Hokkaido University
• Principal Investigator: Ho Hsinjung 北海道大学, 保健科学研究院, 特任講師 (50815561)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Mitochondria / chronic kidney disease / mitochondria / kidney / lipid / cardiolipin / mitofilin / gut microbial status / uremic toxins / SGLT1 / Mitochondrial disease / biomarker / MA-5

Outline of Final Research Achievements

For seeking a novel therapeutic approach for the treatment of mitochondria disorder, several studies have been performed. First, the function of mitofilin, which play an indispensable role in the maintenance of mitochondrial function. Second, for the reason of high mitochondrial content and oxygen consumption in the kidney, the continuous mitochondrial dysfunction plays an essential role in progression of renal diseases. Here, we also investigated a new candidate drug for chronic kidney disease and focused on the correlation between lipotoxicity and mitochondrial dysfunction in the kidney.
The current study found that a SGLT1 inhibitor decreased the accumulated uremic toxins in the renal failure mice, through altering the gut microbiota composition without changing renal function. Moreover, using a proximal tubule epithelial cell line, lipid droplets accumulated in fatty acids treated cells accompanied by decreased ATP production and mitochondrial dysfunction.

Academic Significance and Societal Importance of the Research Achievements

本研究では、腸内細菌叢の変化により腎障害の改善作用や、腎臓の近位尿細管細胞の脂肪滴の減少により、活性酸素種の消去およびミトコンドリア障害の改善作用を示した、将来的にはミトコンドリアのエネルギー代謝機構を解明することで、新たな治療戦略になり、あるいは新たなバイオマーカーを見つけることができると考え、ミトコンドリア病や腎疾患の患者の減少、医療費削減に貢献することができると考える。

Research Products

• [Presentation] SGLT1阻害による腸内細菌叢ならびに代謝物変化の解析 (2018)
  • Author(s): 何 欣蓉、金光 祥臣、三枝 大輔、菊地 晃一、南都 文香、三島 英換、及川 善嗣、松橋 徹郎、秋山 由雅子、鈴木 千登世、鈴木 健弘、伊藤 貞嘉、富岡 佳久、阿部 高明
  • Organizer: Uremic toxin研究会
• [Presentation] Alteration of gut microbiota by SGLT1 inhibitor may reduce uremic toxins in adenine-induced CKD mouse (2018)
  • Author(s): Hsin-Jung Ho, Yoshitomi Kanemitsu, Daisuke Saigusa, Koichi Kikuchi, Fumika Nanto, Eikan Mishima, Yoshitsugu Oikawa, Tetsuro Matsuhashi, Yukako Akiyama, Chitose Suzuki, Takehiro Suzuki, Sadayoshi Ito, Yoshihisa Tomioka and Takaaki Abe
  • Organizer: 日本腎臓学会