| 研究課題/領域番号 |
18K15698
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| 研究機関 | 北海道大学 |
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研究代表者 |
何 欣蓉 北海道大学, 保健科学研究院, 助教 (50815561)
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| 研究期間 (年度) |
2018-04-01 – 2020-03-31
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| キーワード | mitochondria / mitofilin / chronic kidney disease / gut microbial status / uremic toxins / SGLT1 |
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| 研究実績の概要 |
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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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
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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| 今後の研究の推進方策 |
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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| 次年度使用額が生じた理由 |
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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