Roles of VEGF type 1 receptor signaling in pathologicalangiogenesis/lymphangiogenesis

VEGF 1 型受体信号传导在病理性血管生成/淋巴管生成中的作用

• 批准号: 21390072
• 负责人: MAJIMA Masataka
• 金额: $ 11.9万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390072/
• 关键词: 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

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.

血管内皮生长因子（VEGF）被称为主要的血管生成因子，VEGF有3种受体，即VEGFR1（Flt-1）、VEGFR2（Flk-1/KDR）和VEGFR3（Flt-4）。细胞因子介导的血小板 SDF-1 释放量和非内皮 CXCR4+ VEGFR1+ 造血细胞的募集我们测试了 Flt-1 酪氨酸激酶 (TK) 信号通过刺激骨髓干细胞的干细胞因子 (SCF) 和 MMP-9 来增强血管生成。与 WT 相比，TKKO 中 SCF 和 pro-MMP9 的血浆浓度显着降低，两者中 VEGF 的浓度没有显着差异。但在 TKKO 中，血小板沉积的微血管密度被显着抑制。这些结果表明，Flt-1 信号传导对于急性缺血性疾病的恢复至关重要，并且可能有助于治疗缺血。成为再生心血管医学的一种新型治疗策略。

项目成果

Thromboxane A_2 receptor signaling facilitates tumor colonization through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells

血栓素 A_2 受体信号传导通过 P-选择素介导的肿瘤细胞与血小板和内皮细胞的相互作用促进肿瘤定植

• DOI: 10.1111/j.1349-7006.2012.02200.x
• 发表时间: 2012
• 影响因子: 5.7
• 作者: Matsui Y; Amano H; Ito Y; Eshima K; Suzuki T; Ogawa F; Iyoda A; Satoh Y; Kato S; Nakamura M; Kitasato H; Narumiya S; Majima M
• 通讯作者: Majima M

Role of COX-2 in lymphangiogenesis and restoration of lymphatic flow in secondary lymphedema

COX-2 在继发性淋巴水肿淋巴管生成和淋巴液流恢复中的作用

• 发表时间: 2011
• 影响因子: 5
• 作者: Kashiwagi S; Hosono K; Suzuki T; Takeda A; Uchinuma E; Majima M
• 通讯作者: Majima M

The inducible prostaglandin E synthase mPGES-1 regulates growth of endometrial tissues and angiogenesis in a mouse implantation model

诱导型前列腺素 E 合酶 mPGES-1 调节小鼠着床模型中子宫内膜组织的生长和血管生成

• DOI: 10.1016/j.biopha.2010.12.008
• 发表时间: 2011
• 影响因子: 7.5
• 作者: Numao A; Hosono K; Suzuki T; Hayashi I; Uematsu S; Akira S; Ogino Y; Kawauchi H; Unno N; Majima M
• 通讯作者: Majima M

Roles of prostaglandin E2-EP1 receptor signaling in regulation of gastric motor activity and emptying

前列腺素 E2-EP1 受体信号在胃运动活动和排空调节中的作用

• DOI: 10.1152/ajpgi.00524.2009
• 发表时间: 2010
• 作者: Mizuguchi S; Ohno T; Hattori Y; Ae T; Minamino T; Satoh T; Arai K; Saeki T; Hayashi I; Sugimoto Y; Narumiya S; Saigenji K; Majima M
• 通讯作者: Majima M

Estimating the contribution of genes to variation in renal drug clearance by active secretion using multiple data from clinical phase I studies.

使用临床 I 期研究的多个数据估计基因对主动分泌引起的肾脏药物清除率变化的贡献。

• 发表时间: 2010
• 作者: Fujita T; Kumagai Y; Nakahara I; Ohtani Y; Majima M.
• 通讯作者: Majima M.