Examination of inhibition effect by monosaccharide analog for renal cyst progression in polycystic kidney disease
| Project/Area Number |
18K08257
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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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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
Nakajima Kazuki 藤田医科大学, 共同利用研究設備サポートセンター, 講師 (10442998)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 嚢胞性腎疾患群 / 糖脂質 / グルコース代謝 / 糖ヌクレオチド / グライコミクス / メタボロミクス / 細胞増殖 / 嚢胞性腎疾患 / 糖鎖修飾 / グルコシルセラミド / O-GlcNAc化 / マンノース代謝 / 多発性嚢胞腎 / グルコース化脂質 / O-GlcNAc |
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| Outline of Final Research Achievements |
Polycystic kidney disease is characterized by the progressive development of kidney and liver cysts. In this study, I elucidated how treatment with a modified sugar analog disrupts a biological pathway, which in turn block cyst progression.
6-alkynyl fucose was thought to block liver cyst progression via glycan changes, in contrast, 6-azido xylose blocked cell progression in renal cyst-derived cell lines. As other targets, 2-deoxyglucose and Venglustat, inhibitors of glucose metabolism and glycosphingolipid synthesis, cooperatively blocked the cell progression in the cyst-derived cells. Moreover, I identified novel monosaccharide-activated nucleotide sugars (GDP-2-deoxy-mannose and UDP-mannose) as key regulators in glycosylation. Therefore, our hypothesis will provide novel therapeutic targets and valuable insights regarding the molecular mechanisms in polycystic kidney diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
嚢胞性腎疾患群に対する薬物治療法は、唯一トルバプタンのみであり新たな治療方法の確立が望まれている。今回の研究で検討した単糖代謝阻害剤は、その阻害剤の効果を高めることで新たなシード化合物になりえる。また、その阻害剤と別経路の糖脂質代謝阻害剤さらにトルバプタンの併用は、実臨床に近い薬剤を組み合わせた新たな併用療法につながると考えている。さらに今回の研究で検出された希少糖ヌクレオチドは、糖鎖修飾の新たな制御因子になりうることから、嚢胞腎研究や生化学研究において新たな発展が期待される。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Analysis of O-glycoforms of the IgA1 hinge region by sequential deglycosylation.2020
Author(s)
Ohyama Y, Yamaguchi H, Nakajima K, Mizuno T, Fukamachi Y, Yokoi Y, Tsuboi N, Inaguma D, Hasegawa M, Renfrow MB, Novak J, Yuzawa Y, Takahashi K.
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Journal Title
Sci Rep.
Volume: 10(1)
Issue: 1
Pages: 671-671
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Free Glycans Derived From O-mannosylated Glycoproteins Suggest the Presence of an O-glycoprotein Degradation Pathway in Yeast2019
Author(s)
Hirayama H, Matsuda T, Tsuchiya Y, Oka R, Seino J , Huang C, Nakajima K , Noda Y, Shichino Y, Iwasaki S , Suzuki T
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Journal Title
J Biol Chem
Volume: 294(44)
Issue: 44
Pages: 15900-15900
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mass spectrometry-based approach for development of biomarkers in IgA nephropathy: a pilot trial2018
Author(s)
Kondo A, Takahashi K, Yamaguchi H, Yoshida Y, Mizuno T, Nakajima K, Hayashi H, Koide S, Inaguma D, Hasegawa M, Hiki Y, Yuzawa Y
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Journal Title
Fujita Medical Journal
Volume: 4
Pages: 36-41
NAID
Related Report
Peer Reviewed
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