PTB-associated splicing factor inhibits IGF-1-induced VEGF upregulation in a mouse model of oxygen-induced retinopathy
| Autor: | Yan Zhang, Hong Zhang, Wenbo Li, Xiaorong Li, Lijie Dong, Fang Tian, Yan Shao, Hong Nian, Xiaomin Zhang, Yue Yi, Fei Wang, Qiutang Li |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Histology Angiogenesis Retinal Neovascularization Biology Pathology and Forensic Medicine Neovascularization Mice chemistry.chemical_compound Splicing factor Downregulation and upregulation medicine Animals Insulin-Like Growth Factor I PTB-Associated Splicing Factor Gene knockdown RNA-Binding Proteins Cell Biology Transfection Up-Regulation Oxygen Vascular endothelial growth factor Disease Models Animal chemistry Cancer research Female Ectopic expression medicine.symptom Signal Transduction |
| Zdroj: | Cell and Tissue Research. 360:233-243 |
| ISSN: | 1432-0878 0302-766X |
| DOI: | 10.1007/s00441-014-2104-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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