BMP9 and BMP10 are critical for postnatal retinal vascular remodeling

Nicolas Ricard, Delphine Ciais, Sandrine Levet, Mariela Subileau, Christine Mallet, Teresa A. Zimmers, Se Jin Lee, Marie Bidart, Jean Jacques Feige, Sabine Bailly

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

ALK1 is a type I receptor of the TGF-β family that is involved in angiogenesis. Circulating BMP9 was identified as a specific ligand for ALK1 inducing vascular quiescence. In this work, we found that blocking BMP9 with a neutralizing antibody in newborn mice significantly increased retinal vascular density. Surprisingly, Bmp9-KO mice did not show any defect in retinal vascularization. However, injection of the extracellular domain of ALK1 impaired retinal vascularization in Bmp9-KO mice, implicating another ligand for ALK1. Interestingly, we detected a high level of circulating BMP10 in WTand Bmp9-KO pups. Further, we found that injection of a neutralizing anti-BMP10 antibody to Bmp9-KO pups reduced retinal vascular expansion and increased vascular density, whereas injection of this antibody to WT pups did not affect the retinal vasculature. These data suggested that BMP9 and BMP10 are important in postnatal vascular remodeling of the retina and that BMP10 can substitute for BMP9. In vitro stimulation of endothelial cells by BMP9 and BMP10 increased the expression of genes involved in the Notch signaling pathway (Jagged1, Dll4, Hey1, Hey2, Hes1) and decreased apelin expression, suggesting a possible cross-talk between these pathways and the BMP pathway.

Original languageEnglish (US)
Pages (from-to)6162-6171
Number of pages10
JournalBlood
Volume119
Issue number25
DOIs
StatePublished - Jun 21 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Ricard, N., Ciais, D., Levet, S., Subileau, M., Mallet, C., Zimmers, T. A., Lee, S. J., Bidart, M., Feige, J. J., & Bailly, S. (2012). BMP9 and BMP10 are critical for postnatal retinal vascular remodeling. Blood, 119(25), 6162-6171. https://doi.org/10.1182/blood-2012-01-407593