2018 Fiscal Year Research-status Report
Identification and clinical implication of biomarkers for mitochondrial diseases
| Project/Area Number |
18K15698
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| Research Institution | Hokkaido University |
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Principal Investigator |
何 欣蓉 北海道大学, 保健科学研究院, 助教 (50815561)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | mitochondria / mitofilin / chronic kidney disease / gut microbial status / uremic toxins / SGLT1 |
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| Outline of Annual Research Achievements |
For seeking the novel biomarkers for mitochondrial diseases, the study investigated the function of mitochondrial protein, mitofilin. Previous studies proposed that mitofilin is indispensable for normal mitochondrial function. However, the study used the novel drug MA-5 which our group recently invented for investigating the role of mitofilin and the effect of MA-5 in transfected cells (mitofilin overexpression and knockdown).
On the other hand, mitochondrial disorder might cause various diseases, including chronic kidney disease (CKD). Recent studies have revealed significant changes in the composition of the microbial flora in mitochondrial diseases and CKD patients. We also found that inhibition of intestinal sodium/glucose co-transporter (SGLT) 1 can influence the gastrointestinal environment.
According to our recent studies, we examined the effect of a SGLT 1 inhibitor (mizagliflozin) on the uremic toxins in the renal failure mice. The data revealed that the gut-derived uremic toxins reduced and the gut microbiota composition altered by mizagliflozin treatment in renal failure mice without changing renal function. These results suggest that SGLT1 inhibition reduced the accumulation of gut-derived uremic toxins through modification of the gut microbiota, providing a novel and potential therapeutic tool for CKD patients.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The foundation is transferred from Tohoku University to Hokkaido University, due to the reason, the research issue is modified according to equipment of the new research institution. However, the work related to mitochondrial disorder and chronic kidney disease will be continued.
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| Strategy for Future Research Activity |
The further study will focus on the relationship between lipotoxicity and mitochondrial dysfunction in the kidney.
Recent study indicated that cholesteryl ester is accumulated in the urine of chronic kidney disease patients. The accumulated lipids induce mitochondrial dysfunction in the kidney, however, the differences of fatty acids for lipid droplets formation and accumulation are still unknow.
Using a proximal tubule epithelial cell line, HK-2, the effect of lipotoxicity on renal mitochondria and the protective effects of MA-5 on lipid-induced mitochondrial dysfunction will be investigated. We will seek new biomarkers for the diagnosis, for renal diseases patient with mitochondrial dysfunction.
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| Causes of Carryover |
The research institution is transferred from Tohoku University to Hokkaido University in February 2019. During the transference, the incurring amount is occurred, however the incurring amount will be used next year according to the equipment of the new research institution.
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[Presentation] Alteration of gut microbiota by SGLT1 inhibitor may reduce uremic toxins in adenine-induced CKD mouse2018
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
