Therapeutic Potential of Anti-Midkine Therapy in Progressive Renal Diseases
| Project/Area Number |
15590849
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
YUZAWA Yukio Nagoya University, Graduate School of Medicine, Assistant professor, 大学院・医学系研究科, 講師 (00191479)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Seiichi Nagoya University, Graduate School of Medicine, professor, 大学院・医学系研究科, 教授 (70190410)
KADOMATSU Kenji Nagoya University, Graduate School of Medicine, professor, 大学院・医学系研究科, 教授 (80204519)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Midkine / anti-sense ODN / apoptosis / Cisplatin / tubulointerstitial injury / DM / glomerulosclerosis / ERK / I型糖尿病 |
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| Research Abstract |
The following experiments have been performed in order to clarify the potential of midkine(MK) as a candidate of molecular target for the prevention of progressive renal diseases.
(1)The inhibitory effects of MK antisense oligodeoxinucleotide(ODN) "in vivo" in sevelal animal models of renal injuries, such as ischemic renal reperfusion injury, cysplatin nephropathy and STZ induced DM model.
(2)The signal pathway of MK-dependent expression of MCP-1 and MIP-2 in cultured mesangial cells and renal tubular epithelial cells.
(3)The profile of the genes which are up-regulated or down-regulated after stimulation with MK by DNA tip analysis.
RESULTS
(1)Intravenous injection of MK antisense-ODN preferentially incorporated in the proximal tubules in the kidney, and significantly inhibited the expression of MK in the proximal tubules. Furthermore, MK antisense-ODN successfully inhibited the process of progressive renal injuries in ischemic renal reperfusion injury, and cysplatin nephropathy.
(2)In STZ induced DM model, expression of MK in glomeruli was increased The level of glomerular sclerosis which was prominent in wild type mice was much less in MK knockout mice, showing that MK involves in the process of diabetic nephrosclerosis. Further studies showed that MK contributes to the glomerular sclerosis by activation of PKCb and ARK, and by enhancement of macrophage influx in glomeruli.
(3)The urinary excretion of MK in DM patients was well correlated with the pathological stage of DM nephropathy.
These results strongly suggest the prominent potential of MK as a candidate of molecular target for the prevention of progressive renal diseases. The signal pathway through MK and its receptors (LRP and Megalin) would be important for the clinical application of anti-MK therapy.
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Report
(3 results)
Research Products
(18 results)
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[Journal Article] Geranylgeranylacetone Ameliorates Ischemic Acute Renal Failure via Induction of Hsp70.2005
Author(s)
Satoshi Suzuki, Shoichi Maruyama, Waichi Sato, Yoshiki Morita, Fumihiko Sato, Yusuke Miki, Sawako Kato, Masahisa Katsuno, Gen Sobue, Yukio Yuzawa, Seiichi Matsuo
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Journal Title
Kidney International (in press)
Description
「研究成果報告書概要(欧文)」より
Related Report
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