Critical role of caveolin-1 in ocular neovascularization and multitargeted antiangiogenic effects of cavtratin via JNK
| Autor: | Yizhi Liu, Qishan Chen, Xianchai Lin, Rong Ju, Fan Zhang, Zhongshu Tang, Geng Tian, Yihai Cao, Yuxiang Du, Xiangrong Ren, William C. Sessa, Zhiqin Gao, Xiangke Yin, Lijuan Huang, Chunsik Lee, Zhimin Ye, Wei Chen, Shasha Wang, Bin Wang, Jia Mi, Xuri Li, Liying Xing, Yida Jiang |
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| Rok vydání: | 2017 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine medicine.medical_specialty genetic structures MAP Kinase Kinase 4 Angiogenesis Caveolin 1 Angiogenesis Inhibitors Inflammation Retinal Neovascularization Neovascularization 03 medical and health sciences Enos medicine Animals Humans Mice Knockout Multidisciplinary biology Microglia business.industry Antibodies Monoclonal Biological Sciences biology.organism_classification Choroidal Neovascularization Peptide Fragments eye diseases Surgery Vascular endothelial growth factor A 030104 developmental biology Choroidal neovascularization medicine.anatomical_structure cardiovascular system Cancer research Drug Therapy Combination sense organs medicine.symptom business |
| Zdroj: | Proceedings of the National Academy of Sciences. 114:10737-10742 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization. Importantly, combined administration of cavtratin and anti-VEGF-A inhibited neovascularization more effectively than monotherapy, suggesting the existence of other pathways inhibited by cavtratin in addition to VEGF-A. Indeed, we found that cavtratin suppressed multiple critical components of pathological angiogenesis, including inflammation, permeability, PDGF-B and endothelial nitric oxide synthase expression (eNOS). Mechanistically, we show that cavtratin inhibits CNV and the survival and migration of microglia and macrophages via JNK. Together, our data demonstrate the unique advantages of cavtratin in antiangiogenic therapy to treat neovascular diseases. |
| Databáze: | OpenAIRE |
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