A VEGF/JAK2/STAT5 axis may partially mediate endothelial cell tolerance to hypoxia
A VEGF/JAK2/STAT5 axis may partially mediate endothelial cell tolerance to hypoxia
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DOI：
10.1042/bj20050351
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发表时间：
2005-09-01
影响因子：
4.1
通讯作者：
Jenkins, A
中科院分区：
文献类型：
--
作者：
Dudley, AC;Thomas, D;Jenkins, A
氧流的扰动发生在诸如糖尿病视网膜病变和癌症的疾病状态中。为了维持氧稳态，哺乳动物的微血管内皮细胞经历了戏剧性的重组，以帮助将氧气和营养物质带到缺氧组织。这一过程被称为血管生成，常见于某些具有缺氧病灶的癌症和糖尿病视网膜中的局灶性缺血区域。在本研究中，我们报告的激活JAK 2/STAT 5通路（其中JAK代表Janus激酶和STAT代表信号转导和转录激活因子）的微血管内皮细胞中的低氧。这种激活似乎发生在VEGF（血管内皮生长因子）（一种众所周知的促血管生成因子）的下游，并与促凋亡FAS（CD 95）/FASL（CD 95 L）的抑制有关。这些结果表明，JAK/STAT途径可能在肿瘤相关或视网膜血管生成过程中发挥关键作用，其中组织缺氧期间内皮细胞存活对于维持肿瘤生长或糖尿病视网膜病变中常见的不适当视网膜新生血管形成至关重要。
Perturbation of oxygen flow occurs in disease states such as diabetic retinopathy and cancer. To maintain oxygen homoeostasis, the mammalian microvascular endothelium undergoes a dramatic reorganization to assist in bringing oxygen and nutrients to oxygen-starved tissues. This process is termed angiogenesis and is common in certain cancers with hypoxic foci and in areas of focal ischaemia in the diabetic retina. In the present study, we report on the activation of the JAK2/STAT5 pathway (where JAK stands for Janus kinase and STAT stands for signal transduction and activator of transcription) by low oxygen in microvascular endothelial cells. This activation appears to occur downstream of VEGF (vascular endothelial growth factor), a well-known proangiogenic factor, and is related to repression of proapoptotic FAS(CD95)/FASL(CD95L). These results indicate that the JAK/STAT pathway may play a pivotal role during tumour-associated or retinal angiogenesis in which endothelial cell survival during tissue hypoxia is critical for maintaining either the growth of neoplasms or the inappropriate retinal neovascularization common in diabetic retinopathy.