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| Content Provider | Springer Nature Link |
|---|---|
| Author | Dong, Lijie Nian, Hong Shao, Yan Zhang, Yan Li, Qiutang Yi, Yue Tian, Fang Li, Wenbo Zhang, Hong Zhang, Xiaomin Wang, Fei Li, Xiaorong |
| Copyright Year | 2015 |
| Abstract | Pathological retinal neovascularization, including retinopathy of prematurity and age-related macular degeneration, is the most common cause of blindness worldwide. Insulin-like growth factor-1 (IGF-1) has a direct mitogenic effect on endothelial cells, which is the basis of angiogenesis. Vascular endothelial growth factor (VEGF) activation in response to IGF-1 is well documented; however, the molecular mechanisms responsible for the termination of IGF-1 signaling are still not completely elucidated. Here, we show that the polypyrimidine tract-binding protein-associated splicing factor (PSF) is a potential negative regulator of VEGF expression induced by IGF stimulation. Functional analysis demonstrated that ectopic expression of PSF inhibits IGF-1-stimulated transcriptional activation and mRNA expression of the VEGF gene, whereas knockdown of PSF increased IGF-1-stimulated responses. PSF recruited Hakai to the VEGF transcription complex, resulting in inhibition of IGF-1-mediated transcription. Transfection with Hakai siRNA reversed the PSF-mediated transcriptional repression of VEGF gene transcription. In summary, these results show that PSF can repress the transcriptional activation of VEGF stimulated by IGF-1 via recruitment of the Hakai complex and delineate a novel regulatory mechanism of IGF-1/VEGF signaling that may have implications in the pathogenesis of neovascularization in ocular diseases. |
| Starting Page | 233 |
| Ending Page | 243 |
| Page Count | 11 |
| File Format | |
| ISSN | 0302766X |
| Journal | Cell and Tissue Research |
| Volume Number | 360 |
| Issue Number | 2 |
| e-ISSN | 14320878 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2015-02-01 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Polypyrimidine tract-binding protein-associated splicing factor (PSF) Insulin-like growth factor-1 (IGF-1) Vascular endothelial growth factor (VEGF) Hakai Retinal neovascularization (RNV) Human Genetics Proteomics Molecular Medicine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Histology Pathology and Forensic Medicine |
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