Development of therapy for malignant tumors and inflammatory diseases employing midkine as a molecular target
| Project/Area Number |
15390103
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Aichi Gakuin University (2004)
Nagoya University (2003) |
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Principal Investigator |
MURAMATSU Takashi Aichi Gakuin University, Faculty of Psychological and Physical Sciences, Department of Health Science, Professor, 心身科学部, 教授 (00030891)
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| Co-Investigator(Kenkyū-buntansha) |
KADOMATSU Kenji Nagoya University Graduate School of Medicine, Department of Biochemistry, Associate Professor, 大学院・医学系研究科, 助教授 (80204519)
MURAMATSU Hisako Nagoya University Graduate School of Medicine, Department of Biochemistry, Associate Professor, 大学院・医学系研究科, 助教授 (50182134)
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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 |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2003: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | midkine / Anti-cancer drug / renal toxicity / knockout mice / neutrophils / tumor metastasis / endothelial cells / antisense oligo DNA / リウマチ / アルツハイマー病 / 新生内膜形成 / 炎症性細胞 / 癒着 / マクロファージ |
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| Research Abstract |
Midkine played important roles in renal injury caused by ischemia or chemotherapeutic reagent. Promotion of migration of inflammatory leukocytes was the primary mechanism of midkine action. We injected midkine antisense oligo DNA to tail vein of mice to suppress midkine expression. The oligo DNA was actively taken up by renal tubular epithelial cells. When oligo DNA was injected before ischemia or drug administration, migration of inflammatory leukocytes to renal tubules was significantly suppressed. Sense oligo DNA did not exhibited the effects. Furthermore, renal damage by ischemia was indeed lessened by the oligo DNA treatment. Neointima formation after injury was also lessened by prior treatment with the antisense oligo DNA.
The involvement of midkine in adhesions after surgery and arthritis after injection of anti-type II collagen, a model of rheumatoid arthritis. was shown by using mice deficient in the midkine gene. In both cases, promotion of migration of inflammatory leukocytes is involved ; in addition midkine promoted differentiation of osteoclasts in the case of arthritis.
We developed antisense oligo DNA and siRNA to suppress the expression of human midkine. We also found that atelocollagen helped both stabilization and incorporation of siRNA, and verified the effects by suppressing VBGF expression leading to the growth suppression of nude-mice grown human tumors. The involvement of midkine in host blood vessels in tumor metastasis was demonstrated by using mice deficient in the midkine gene.
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Report
(3 results)
Research Products
(21 results)
