| Project/Area Number |
26461223
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
KUME Shinji 滋賀医科大学, 医学部, 助教 (00452235)
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| Research Collaborator |
TANAKA Yuki
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 慢性腎臓病 / 蛋白尿 / 脂肪毒性 / NAD代謝 / 糖尿病性腎症 / アポトーシス / 慢性腎不全 / 1-MNA / NNMT |
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| Outline of Final Research Achievements |
Free fatty acid-bound albumin (FFA-albumin) is involved in the pathogenesis of proteinuric chronic kidney diseases (CKD). Nicotinamide adenine dinucleotide (NAD) metabolism has recently been focused as a novel therapeutic target for several modern diseases. This study was designed to identify a novel molecule in NAD metabolism to protect kidneys from lipotoxicity. Among 19 candidate enzymes involved in mammalian NAD metabolism, the mRNA expression level of nicotinamide n-methyltransferase (NNMT) was significantly increased in both the kidneys of FFA-albumin-overloaded mice and cultured cells stimulated with FFA-albumin. Overexpression of NNMT and 1-MNA, the metabolite of NNMT, inhibited FFA-albumin-induced cell death. Furthermore, oral administration of 1-MNA ameliorated kidney injury in FFA-albumin-overloaded mice. In conclusion, NNMT-derived 1-MNA can reduce renal lipotoxicity. Supplementation of 1-MNA may have potential as a new therapy in CKD patients with refractory proteinuria.
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