| Project/Area Number |
21390072
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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 |
General pharmacology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
FUJITA Tomoe 北里大学, 医学部, 講師 (20296510)
KAWAMURA Michiko 北里大学, 医学部, 助教 (00154104)
AMANO Hideki 北里大学, 医学部, 講師 (60296481)
SUZUKI Tatsunori 北里大学, 医学部, 助教 (70406940)
KITASATO Hidero 北里大学, 医療衛生学部, 教授 (90195256)
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| Project Period (FY) |
2009 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2010: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2009: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 血管新生 / リンパ管新生 / VEGF / 1 型受容体 / ノックアウトマウス / 病態モデル / Gene targeting / 骨髄由来細胞 / VEGFR-1シグナリング / 肺再生 / 肺胞上皮細胞 / VEGFR1チロシンキナーゼノックアウトマウス / 1型受容体 / 肝修復 / がん / 慢性炎症 / 血小板 / VEGF 1型受容体 / アセトアミノフェン / 肝障害 / 類洞 / マクロファージ / 血管内皮細胞 / 肝細胞 / 血管内皮細胞増殖因子 / tyrosin kinase / 後肢虚血モデル / 潰瘍治癒モデル / 創傷治癒モデル / 骨髄機能 |
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| Research Abstract |
Vascular endothelial growth factor (VEGF) is known as a major propangiogenic factor. VEGF has 3 receptors, namely VEGFR1 (Flt-1), VEGFR2 (Flk-1/KDR) and VEGFR3 (Flt-4). We had previously reported that the magnitude of cytokine-mediated release of SDF-1 from platelets and the recruitment of nonendothelial CXCR4+ VEGFR1+ hematopoietic progenitors, ‘hemangiocytes,’ constitute the major determinant of angiogenesis. We tested that Flt-1 Tyrosine Kinase (TK) signaling enhances angiogenesisby stimulating Stem Cell Factor (SCF) and MMP-9 by bone marrow stem cells. Blood flow recovery in TKKO was significantly delayed compared to WT. Compared to WT, plasma concentrations of SCF and pro-MMP9 were significantly reduced in TKKO. There was no significant difference between the concentrations of VEGF in both mice, but in TKKO, platelets-deposited microvascular density was significantly suppressed. These results suggested that the signaling of the Flt-1 is essential for recovering from acute ischemic conditions. Administration of selective VEGFR1 agonist may be useful to treat the ischemia, and may become a novel therapeutic strategy in regenerative cardiovascular medicine.
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