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ZFIN ID: ZDB-PUB-140914-1
GPR126 Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Signaling
Cui, H., Wang, Y., Huang, H., Yu, W., Bai, M., Zhang, L., Bryan, B.A., Wang, Y., Luo, J., Li, D., Ma, Y., Liu, M.
Date: 2014
Source: The Journal of biological chemistry   289(50): 34871-85 (Journal)
Registered Authors: Huang, Huizhe
Keywords: G protein-coupled receptor (GPCR), VEGFR2, angiogenesis, endothelial cell, protein kinase A (PKA), vascular endothelial growth factor (VEGF)
MeSH Terms:
  • Animals
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Cyclic AMP/metabolism
  • Embryonic Development
  • Endothelial Cells/cytology
  • Endothelial Cells/drug effects
  • GATA2 Transcription Factor/metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • Mice
  • Neovascularization, Pathologic/genetics
  • Neovascularization, Pathologic/metabolism*
  • Neovascularization, Pathologic/pathology*
  • Receptors, G-Protein-Coupled/deficiency
  • Receptors, G-Protein-Coupled/genetics
  • Receptors, G-Protein-Coupled/metabolism*
  • STAT5 Transcription Factor/metabolism
  • Signal Transduction*
  • Transcription, Genetic
  • Vascular Endothelial Growth Factor Receptor-2/metabolism*
  • Zebrafish/embryology
PubMed: 25217645 Full text @ J. Biol. Chem.
Angiogenesis, the formation of new blood vessels from preexisting ones, is essential for development, wound healing, and tumor progression. The VEGF pathway plays irreplaceable roles during angiogenesis, but how other signals crosstalk with and modulate VEGF cascades is not clearly elucidated. Here, we identified that Gpr126, an endothelial cell enriched gene, plays an important role in angiogenesis by regulating endothelial cell proliferation, migration, and tube formation. Knockdown of Gpr126 in the mouse retina resulted in the inhibition of hypoxia-induced angiogenesis. Interference of Gpr126 expression in zebrafish embryos led to defects in intersegmental vessel formation. Finally, we identified that GPR126 regulated the expression of VEGFR2 by targeting STAT5 and GATA2 through the cAMP-PKA-CREB signaling pathway during angiogenesis. Our findings illustrate that GPR126 modulates both physiological and pathological angiogenesis through VEGF signaling, providing a potential target for the treatment of angiogenesis-related diseases.