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.
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Research Article|
August 23 2005
A VEGF/JAK2/STAT5 axis may partially mediate endothelial cell tolerance to hypoxia
Andrew C. Dudley;
Andrew C. Dudley
1
1Department of Medicine, St. Vincent's Hospital, University of Melbourne, Corner of Princes and Regent Streets, Fitzroy, VIC, 3065, Australia
1Present address and address for correspondence: Harvard Medical School, Karp Family Research Laboratories, 12th Floor, Children's Hospital, 300 Longwood Ave., Boston, MA 02115-5737, U.S.A. (email andrew.dudley@childrens.harvard.edu).
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David Thomas;
David Thomas
1Department of Medicine, St. Vincent's Hospital, University of Melbourne, Corner of Princes and Regent Streets, Fitzroy, VIC, 3065, Australia
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James Best;
James Best
1Department of Medicine, St. Vincent's Hospital, University of Melbourne, Corner of Princes and Regent Streets, Fitzroy, VIC, 3065, Australia
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Alicia Jenkins
Alicia Jenkins
1Department of Medicine, St. Vincent's Hospital, University of Melbourne, Corner of Princes and Regent Streets, Fitzroy, VIC, 3065, Australia
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Publisher: Portland Press Ltd
Received:
February 28 2005
Revision Received:
May 13 2005
Accepted:
May 27 2005
Accepted Manuscript online:
May 27 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 390 (2): 427–436.
Article history
Received:
February 28 2005
Revision Received:
May 13 2005
Accepted:
May 27 2005
Accepted Manuscript online:
May 27 2005
Citation
Andrew C. Dudley, David Thomas, James Best, Alicia Jenkins; A VEGF/JAK2/STAT5 axis may partially mediate endothelial cell tolerance to hypoxia. Biochem J 1 September 2005; 390 (2): 427–436. doi: https://doi.org/10.1042/BJ20050351
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