PUBLICATION
Nuclear translocation of cGAS orchestrates VEGF-A-mediated angiogenesis
- Authors
- Luo, J., Lu, C., Chen, Y., Wu, X., Zhu, C., Cui, W., Yu, S., Li, N., Pan, Y., Zhao, W., Yang, Q., Yang, X.
- ID
- ZDB-PUB-230408-45
- Date
- 2023
- Source
- Cell Reports 42: 112328112328 (Journal)
- Registered Authors
- Chen, Yang, Lu, Chunjiao, Luo, Juanjuan, Wu, Xuewei, Yang, Xiaojun
- Keywords
- ARPC3, CP: Cell biology, VEGF-A, VEGFR2, angiogenesis, cGAS, zebrafish
- MeSH Terms
-
- Cytosol/metabolism
- DNA/metabolism
- Humans
- Immunity, Innate
- MicroRNAs*/metabolism
- Nucleotidyltransferases/metabolism
- Signal Transduction
- Vascular Endothelial Growth Factor A*/metabolism
- PubMed
- 37027305 Full text @ Cell Rep.
Citation
Luo, J., Lu, C., Chen, Y., Wu, X., Zhu, C., Cui, W., Yu, S., Li, N., Pan, Y., Zhao, W., Yang, Q., Yang, X. (2023) Nuclear translocation of cGAS orchestrates VEGF-A-mediated angiogenesis. Cell Reports. 42:112328112328.
Abstract
Cyclic GMP-AMP synthase (cGAS) senses cytosolic incoming DNA and consequently activates stimulator of interferon response cGAMP interactor 1 (STING) to mount immune response. Here, we show nuclear cGAS could regulate VEGF-A-mediated angiogenesis in an immune-independent manner. We found VEGF-A stimulation induces cGAS nuclear translocation via importin-β pathway. Moreover, nuclear cGAS subsequently regulates miR-212-5p-ARPC3 cascade to modulate VEGF-A-mediated angiogenesis through affecting cytoskeletal dynamics and VEGFR2 trafficking from trans-Golgi network (TGN) to plasma membrane via a regulatory feedback loop. In contrast, cGAS deficiency remarkably impairs VEGF-A-mediated angiogenesis in vivo and in vitro. Furthermore, we found strong association between the expression of nuclear cGAS and VEGF-A, and the malignancy and prognosis in malignant glioma, suggesting that nuclear cGAS might play important roles in human pathology. Collectively, our findings illustrated the function of cGAS in angiogenesis other than immune surveillance, which might be a potential therapeutic target for pathological angiogenesis-related diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping