The role of mesangial cells in glomeruli formation and the development of diabetic kidney disease
| Project/Area Number |
16K09619
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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 | The University of Tokushima |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
岸 誠司 徳島大学, 病院, 助教 (10519507)
冨永 辰也 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (80425446)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | メサンギウム細胞 / 糸球体硬化 / 細胞内シグナル伝達 / 糖尿病性腎症 / 慢性腎臓病 / 内科 / 発生・分化 / 糖尿病 / シグナル伝達 |
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| Outline of Final Research Achievements |
In vitro, we could modify the method to harvest mesangial cells from mouse kidney efficiently. In vivo, we could establish the protocol to raise mesangium-specific gene modified mice by a Cre-loxP system. To activate mTORC1-S6 kinase pathway, TSC1 (the upstream inhibitory molecule of the pathway) was deleted in mesangial cells. mTORC1-S6 kinase pathway activation could induce mesangial expansion and sclerotic phenotypic change. We also made the mice which had BMP-4 or TGF-b1 overexpression in glomeruli. BMP-4 could cause the lesion which mimicked human dibaetic kidney disease. The mice which had Wnt/b-catenin pathway activation in mesangial cells were developed. The analysis of the phenotype is in progress.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病性腎症を代表とする慢性腎臓病は透析導入原疾患であるとともに心血管系疾患のリスクが高く、対応が急務であるが、現存の治療法では明らかに不十分である。その進展増悪機構を理解するのに、主に慢性腎臓病の初期に病変がおこるメサンギウム細胞の役割解明は必須であるが、これまでその方法に乏しかった。今回の研究でin vitroにおいてはメサンギウム細胞の効率的な単離培養法が確立された。in vivoではメサンギウム細胞特異的な目標分子の役割をしらべるシステムを確立し、慢性腎臓病の原因の一つを同定することができた。よって新規治療法の確立に大きく寄与すると考えられた。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Urinary IgG4 and Smad1 are Specific Biomarkers for Renal Structural and Functional Changes in Early Stage of Diabetic Nephropathy.2018
Author(s)
Doi T, Moriya T, Fujita Y, Minagawa N, Usami M, Sasaki T, Abe H, Kishi S, Murakami T, Ouchi M, Ichien G, Yamamoto K, Ikeda H, Koezuka Y, Takamatsu N, Shima K, Mauer M, Nagai K, Tominaga T.
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Journal Title
Diabetes
Volume: 67
Issue: 5
Pages: 986-993
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mesangial cell mTORC1 activation results in mesangial expansion2017
Author(s)
Kojiro Nagai, Tatsuya Tominaga, Sayo Ueda, Eriko Shibata, Masanori Tamaki, Motokazu Matsuura, Seiji Kishi, Taichi Murakami, Tatsumi Moriya, Hideharu Abe, Toshio Doi
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Journal Title
Journal of American Society of Nephrology
Volume: 28
Issue: 10
Pages: 2879-2885
DOI
Related Report
Peer Reviewed
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