Elucidation of the regulatory mechanism for glucose-mediated pathogenic gene expression in diabetic nephropathy and its therapeutic application
| Project/Area Number |
24390229
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MAKINO YUICHI 旭川医科大学, 医学部, 准教授 (90345033)
FUJITA YUKIHIRO 旭川医科大学, 医学部, 助教 (20451461)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Keywords | 糖尿病 / 糖尿病性腎症 / 転写因子 / メサンギウム細胞 / 糸球体 / 高グルコース / ChREBP / 遺伝子発現異常 |
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| Outline of Final Research Achievements |
High glucose evokes pathogenic gene expressions in mesangial cells to develop diabetic nephropathy. A glucose responsive transcription factor, carbohydrate response element binding protein (ChREBP), plays a pivotal role in such derangement of gene regulation. To establish a strategy for targeting the effector molecules downstream of ChREBP in diabetic circumstances, we performed chromatin immunoprecipitation with anti-ChREBP antibodies followed by DNA microarray analysis and identified hypoxia-inducible factor-1α, platelet derived growth factor-C, and membrane-bound transcription factor peptidase site1 as novel target genes of ChREBP in mesangial cells exposed to high glucose. Those genes seemed to contribute to the extra cellular matrix expansion in the glomeruli, the regulation of ER-stress of mesangial cells. Targeting the molecules ameliorated gene profiles and pathology of the glomeruli of diabetic mice, indicating a possible therapeutic intervention of diabetic nephropathy.
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Report
(5 results)
Research Products
(11 results)
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[Journal Article] High glucose induces platelet-derived growth factor-C via carbohydrate response element-binding protein in glomerular mesangial cells.2016
Author(s)
Kitsunai H, Makino Y, Sakagami H, Mizumoto K, Yanagimachi T, Atageldiyeva K, Takeda Y, Fujita Y, Abiko A, Takiyama Y, Haneda M.
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Journal Title
Physiol Rep
Volume: 4
Issue: 6
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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