Elucidation of molecular mechanisms and development of vascular complications in diabetic nephropathy and renal arteriosclerosis
| Project/Area Number |
15K09265
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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 |
ABE Hideharu 徳島大学, 大学院医歯薬学研究部(医学系), 准教授 (60399342)
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| Co-Investigator(Kenkyū-buntansha) |
村上 太一 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (30403736)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 糖尿病性腎症 / 腎硬化症 / 腎臓病修復学 / Smad1 / BMP4 / 糸球体硬化 / 糖尿病 / 加齢 / 細胞老化 / 細動脈硬化 |
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| Outline of Final Research Achievements |
In diabetic kidney disease (DKD), incipient diabetic nephropathy is classically defined by increasing albuminuria, heralding a decline in glomerular filtration rate (GFR). However, a proportion of patients with type 2 diabetes does not follow this classical albuminuric pathway. Varying degrees of arteriosclerosis were seen in the subjects with normoalbuminuria. We previously found that Smad1 plays a critical role in the development of DKD both in vitro and in vivo. However, functional interaction between Smad1 and Smad3 signaling in DKD is unclear. Extracellular matrix (ECM) protein overexpression and Smad1 activation were observed in the glomeruli of db/db mice but were suppressed in the glomeruli of Smad3-KO-DKD mice. Smad3 activation enhanced the phosphorylation of Smad1 C-terminal domain but decreased the phosphorylation of linker domain. Collectively, preferential activation of the Smad1 linker domain may provide a novel therapeutic approach for treating DKD.
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Report
(4 results)
Research Products
(7 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] Probucol modulates Nrf2 function and ameliorates diabetic nephropathy in db/db mice.2017
Author(s)
Arai H, Abe H, Sakurai A, Yamashita K, Murayama T, Minami M, Yoshikawa T, Kohashi M, Nozako M, Yokode M, Doi T.
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Journal Title
Medical Research Archives.
Volume: ４
Pages: 1-16
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Bone Morphogenetic Protein 4 and Smad1 Mediate Extracellular Matrix Production in the Development of Diabetic Nephropathy.2015
Author(s)
Matsubara T, Araki M, Abe H, Ueda O, Jishage K, Mima A, Goto C, Tominaga T, Kinosaki M, Kishi S, Nagai K, Iehara N, Fukushima N, Kita T, Arai H, Doi T.
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Journal Title
Diabetes
Volume: ６４
Issue: 8
Pages: 2978-2990
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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