p38 MAP kinase -: a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability
p38 MAP kinase -: a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability
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DOI：
10.1096/fj.02-0329fje
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发表时间：
2002-12-01
期刊：
影响因子：
4.8
通讯作者：
Clauss, M
中科院分区：
文献类型：
--
作者：
Issbrücker, K;Marti, HH;Clauss, M
血管内皮生长因子（VEGF）不仅是血管发生和血管生成所必需的，而且是血管通透性的强诱导剂。虽然血管生成和血管通透性诱导性质之间的分子途径的解剖对于血管生成和抗血管生成疗法的发展是期望的，但是这样的机制尚未被鉴定。在这里，我们提供了p38 MAPK作为分隔这两个过程的信号分子的作用的证据。抑制p38 MAPK活性增强VEGF诱导的血管生成在体外和体内，这一发现是伴随着延长Erk 1/2 MAPK激活，增加内皮细胞存活，和纤溶酶原激活。相反，相同的抑制剂在体外和体内消除VEGF诱导的血管通透性。p38 MAPK的这些双重性质不仅与治疗性血管生成有关，而且与减少水肿形成和增强缺血性疾病中的组织修复有关。
Vascular endothelial growth factor (VEGF) is not only essential for vasculogenesis and angiogenesis but also is a potent inducer of vascular permeability. Although a dissection of the molecular pathways between angiogenesis- and vascular permeability-inducing properties would be desirable for the development of angiogenic and anti-angiogenic therapies, such mechanisms have not been identified yet. Here we provide evidence for a role of the p38 MAPK as the signaling molecule that separates these two processes. Inhibition of p38 MAPK activity enhances VEGF-induced angiogenesis in vitro and in vivo, a finding that was accompanied by prolonged Erk1/2 MAPK activation, increased endothelial survival, and plasminogen activation. Conversely, the same inhibitors abrogate VEGF-induced vascular permeability in vitro and in vivo. These dualistic properties of p38 MAPK are relevant not only for therapeutic angiogenesis but also for reducing edema formation and enhancing tissue repair in ischemic diseases.