In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 103, No. 46 ( 2006-11-14), p. 17260-17265
Abstract:
VEGF and TGF-β1 are potent angiogenesis inducers with opposing effects on endothelial cells. TGF-β1 induces apoptosis; VEGF protects endothelial cells from apoptosis. We found that TGF-β1 promotes endothelial cell expression of FGF-2, which up-regulates VEGF synthesis. Inhibition of VEGF signaling through VEGF receptor 2 (flk-1) abrogates TGF-β1-induced apoptosis and p38 MAPK activation. Inhibition of p38 MAPK blocks TGF-β1-induced apoptosis, showing that VEGF/flk-1-mediated activation of p38 MAPK is required for TGF-β1 induction of apoptosis. In the absence of TGF-β1, VEGF activates p38 MAPK and promotes endothelial cell survival. However, in context with TGF-β1, VEGF/flk-1-mediated activation of p38 MAPK results in apoptosis. Thus, cross-talk between TGF-β1 and VEGF signaling converts VEGF/flk-1-activated p38 MAPK into a proapoptotic signal. This finding illustrates an unexpected role of VEGF and indicates that VEGF can be pharmacologically converted into an apoptotic factor, a novel approach to antiangiogenesis therapy.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0605556103
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2006
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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