The Role of Vascular Endothelial Growth Factor Receptor-1 Signaling in the Recovery from Ischemia.
The Role of Vascular Endothelial Growth Factor Receptor-1 Signaling in the Recovery from Ischemia.
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DOI：
10.1371/journal.pone.0131445
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Majima M
中科院分区：
文献类型：
--
作者：
Amano H;Kato S;Ito Y;Eshima K;Ogawa F;Takahashi R;Sekiguchi K;Tamaki H;Sakagami H;Shibuya M;Majima M
血管内皮生长因子（VEGF）是最有效的血管生成刺激剂之一。 VEGF 与 VEGF 受体 1 (VEGFR1) 结合，通过受体的酪氨酸激酶结构域 (TK) 诱导血管生成，但其机制尚不清楚。我们使用缺血后肢模型研究了 VEGFR1 酪氨酸激酶信号在血管生成中的作用。相对于对照小鼠，用 VEGFA 中和抗体治疗的小鼠的血流恢复明显受损。 VEGFR1 酪氨酸激酶敲除小鼠 (TK-/-) 的缺血血流恢复延迟且血管生成受损，并且这种表型不受 VEGFR2 抑制剂治疗的影响。与野生型小鼠（WT）相比，TK-/-小鼠血浆VEGF水平没有变化，但血浆基质源细胞因子1（SDF-1）和干细胞因子的水平以及基质金属蛋白酶原9（pro-MMP-9）的骨髓（BM）水平显着降低。表达 VEGFR1 和 C-X-C 趋化因子受体 4 型 (CXCR4) 的细胞募集到外周血和缺血肌肉中的情况也受到抑制。此外，与移植有WT BM的WT相比，移植有TK-/- BM的WT显着损害血流恢复。这些结果表明，VEGFR1-TK 信号传导通过从 BM 募集 CXCR4+VEGFR1+ 细胞来促进血管生成。
Vascular endothelial growth factor (VEGF) is one of the most potent angiogenesis stimulators. VEGF binds to VEGF receptor 1 (VEGFR1), inducing angiogenesis through the receptor’s tyrosine kinase domain (TK), but the mechanism is not well understood. We investigated the role of VEGFR1 tyrosine kinase signaling in angiogenesis using the ischemic hind limb model. Relative to control mice, blood flow recovery was significantly impaired in mice treated with VEGFA-neutralizing antibody. VEGFR1 tyrosine kinase knockout mice (TK-/-) had delayed blood flow recovery from ischemia and impaired angiogenesis, and this phenotype was unaffected by treatment with a VEGFR2 inhibitor. Compared to wild type mice (WT), TK-/- mice had no change in the plasma level of VEGF, but the plasma levels of stromal-derived cell factor 1 (SDF-1) and stem cell factor, as well as the bone marrow (BM) level of pro-matrix metalloproteinase-9 (pro-MMP-9), were significantly reduced. The recruitment of cells expressing VEGFR1 and C-X-C chemokine receptor type 4 (CXCR4) into peripheral blood and ischemic muscles was also suppressed. Furthermore, WT transplanted with TK-/- BM significantly impaired blood flow recovery more than WT transplanted with WT BM. These results suggest that VEGFR1-TK signaling facilitates angiogenesis by recruiting CXCR4+VEGFR1+ cells from BM.
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DOI：
10.1084/jem.193.9.1005
发表时间：
2001-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hattori K;Dias S;Heissig B;Hackett NR;Lyden D;Tateno M;Hicklin DJ;Zhu Z;Witte L;Crystal RG;Moore MA;Rafii S
通讯作者：
Rafii S
影响因子：
20.3
作者：
Hattori, K;Heissig, B;Moore, MAS
通讯作者：
Moore, MAS
影响因子：
3.5
作者：
Di, Qun;Cheng, Zeen;Cheng, Xianwu
通讯作者：
Cheng, Xianwu
影响因子：
20.1
作者：
Amano, H;Hackett, NR;Crystal, RG
通讯作者：
Crystal, RG
影响因子：
20.1
作者：
Johnson, C;Sung, HJ;Galis, ZS
通讯作者：
Galis, ZS