Dudley Andrew C, Thomas David, Best James, Jenkins Alicia
Department of Medicine, St. Vincent's Hospital, University of Melbourne, Corner of Princes and Regent Streets, Fitzroy, VIC, 3065, Australia.
Biochem J. 2005 Sep 1;390(Pt 2):427-36. doi: 10.1042/BJ20050351.
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.
在诸如糖尿病视网膜病变和癌症等疾病状态下会发生氧流量紊乱。为维持氧稳态，哺乳动物微血管内皮细胞会发生显著重组，以协助将氧气和营养物质输送到缺氧组织。这个过程被称为血管生成，在某些具有缺氧灶的癌症以及糖尿病视网膜病变的局部缺血区域很常见。在本研究中，我们报道了低氧对微血管内皮细胞中JAK2/STAT5信号通路（其中JAK代表Janus激酶，STAT代表信号转导及转录激活因子）的激活作用。这种激活似乎发生在血管内皮生长因子（VEGF，一种著名的促血管生成因子）下游，并且与促凋亡因子FAS(CD95)/FASL(CD95L)的抑制有关。这些结果表明，JAK/STAT信号通路可能在肿瘤相关或视网膜血管生成过程中起关键作用，在这个过程中，组织缺氧时内皮细胞的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。
