2004 Fiscal Year Final Research Report Summary
Induction and termination of angiogenesis by regulation of angiogenesis-related factor production
| Project/Area Number |
15390020
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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 |
Biological pharmacy
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| Research Institution | Tohoku University |
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Principal Investigator |
HIRASAWA Noriyasu Tohoku University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (80181155)
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| Co-Investigator(Kenkyū-buntansha) |
OHUCHI Kazuo Tohoku University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (20006357)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Angiogenesis / Vascular endothelial growth factor / Angiopoietin-1 / Angiopoietin-2 / Endostatin / Granulation tissue / Histamine / phosphodiesterase IV inhibitor |
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| Research Abstract |
1.Regulation of angiogenesis in granulation tissues was examined using cotton thread-induced proliferative inflammation model in mice. Subcutaneous implantation of a cotton thread in the dorsum of mice induced gradual increase in the hemoglobin content in the granulation tissues from 3 to 7 days. The levels of vascular endothelial growth factor (VEGF) and angiopoietin-1 in the granulation tissues were also increased over the same time points. Then, the hemoglobin content and the level of VEGF in the granulation tissues were decreased from 7 to 28 days. The levels of endostatin and angiopoietin-2 in the granulation tissues were increased at 14 days. These results suggest that VEGF and angiopoietin-1 are involved in the angiogenesis, and angiopoietin-2 and endostatin induce the termination of angiogenesis.
2.In histidine decarboxylase-deficient mice, angiogenesis and maturation of new vessels in the cotton thread-induced granulation tissues were defected. The levels of VEGF and angiopoietin-1 in the granulation tissues in HDC-deficient mice were significantly lower than those in wild-type mice. The injection of anti-VEGF inhibited histamine-induced angiopoietin-1 production, and the injection of VEGF increased angiopoietin-1 level but decreased the levels of angiopoietin-2 and endostatin. These results suggest that histamine induces VEGF production and VEGF up-regulates angiopoietin-1 but down-regulates angiopoietin-2 and endostatin production.
3.We established the screening system using murine macrophage-like cell line RAW264 to find the compound that induces VEGF production, and found that phosphodiesterase IV inhibitors strongly induced VEGF production in macrophages. The compound that induces endogenous VEGF production would be useful for acceleration of wound healing.
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