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- Title
VEGF-B inhibits apoptosis via VEGFR-1--mediated suppression of the expression of BH3-only protein genes in mice and rats.
- Authors
Yang Li; Fan Zhang; Nagai, Nobuo; Zhongshu Tang; Shuihua Zhang; Scotney, Pierre; Lennartsson, Johan; Chaoyong Zhu; Yi Qu; Changge Fang; Jianyuan Hua; Matsuo, Osamu; Guo-Hua Fong; Hao Ding; Yihai Cao; Becker, Kevin G.; Nash, Andrew; Heldin, Carl-Henrik; Xuri Li
- Abstract
Despite its early discovery and high sequence homology to the other VEGF family members, the biological functions of VEGF-B remain poorly understood. We revealed here a novel function for VEGF-B as a potent inhibitor of apoptosis. Using gene expression profiling of mouse primary aortic smooth muscle cells, and confirming the results by real-time PCR using mouse and rat cell lines, we showed that VEGF-B inhibited the expression of genes encoding the proapoptotic BH3-only proteins and other apoptosis- and cell death-related proteins, including p53 and members of the caspase family, via activation of VEGFR-1. Consistent with this, VEGF-B treatment rescued neurons from apoptosis in the retina and brain in mouse models of ocular neurodegenerative disorders and stroke, respectively. Interestingly, VEGF-B treatment at the dose effective for neuronal survival did not cause retinal neovascularization, suggesting that VEGF-B is the first member of the VEGF family that has a potent antiapoptotic effect while lacking a general angiogenic activity. These findings indicate that VEGF-B may potentially offer a new therapeutic option for the treatment of neurodegenerative diseases.
- Subjects
LABORATORY rats; LABORATORY mice; PROTEINS; APOPTOSIS; CELL death
- Publication
Journal of Clinical Investigation, 2008, Vol 118, Issue 3, p913
- ISSN
0021-9738
- Publication type
Article