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Publication : NDRG1 activates VEGF-A-induced angiogenesis through PLCγ1/ERK signaling in mouse vascular endothelial cells.

First Author  Watari K Year  2020
Journal  Commun Biol Volume  3
Issue  1 Pages  107
PubMed ID  32144393 Mgi Jnum  J:288840
Mgi Id  MGI:6433605 Doi  10.1038/s42003-020-0829-0
Citation  Watari K, et al. (2020) NDRG1 activates VEGF-A-induced angiogenesis through PLCgamma1/ERK signaling in mouse vascular endothelial cells. Commun Biol 3(1):107
abstractText  Many diseases, including cancer, have been associated with impaired regulation of angiogenesis, of which vascular endothelial growth factor (VEGF)-A is a key regulator. Here, we test the contribution of N-myc downstream regulated gene 1 (NDRG1) to VEGF-A-induced angiogenesis in vascular endothelial cells (ECs). Ndrg1(-/-) mice exhibit impaired VEGF-A-induced angiogenesis in corneas. Tumor angiogenesis induced by cancer cells that express high levels of VEGF-A was also reduced in a mouse dorsal air sac assay. Furthermore, NDRG1 deficiency in ECs prevented angiogenic sprouting from the aorta and the activation of phospholipase Cgamma1 (PLCgamma1) and ERK1/2 by VEGF-A without affecting the expression and function of VEGFR2. Finally, we show that NDRG1 formed a complex with PLCgamma1 through its phosphorylation sites, and the inhibition of PLCgamma1 dramatically suppressed VEGF-A-induced angiogenesis in the mouse cornea, suggesting an essential role of NDRG1 in VEGF-A-induced angiogenesis through PLCgamma1 signaling.
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