2. Academic Validation
  3. VEGFR2 activation mediates the pro-angiogenic activity of BMP4

VEGFR2 activation mediates the pro-angiogenic activity of BMP4

  • Angiogenesis. 2019 Nov;22(4):521-533. doi: 10.1007/s10456-019-09676-y.
Sara Rezzola 1,  Margherita Di Somma 1,  Michela Corsini 1,  Daria Leali 2,  Cosetta Ravelli 1 3,  Viviane A B Polli 4,  Elisabetta Grillo 1,  Marco Presta 1,  Stefania Mitola 5 6
Affiliations

Affiliations

  • 1 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
  • 2 Azienda Socio-sanitaria Territoriale Spedali Civili di Brescia, Brescia, Italy.
  • 3 Laboratory for Preventive and Personalized Medicine (MPP Lab), University of Brescia, Brescia, Italy.
  • 4 Department of Cellular Biology, Embryology and Genetics, Federal University of Santa Catarina, Florianópolis, Brazil.
  • 5 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. stefania.mitola@unibs.it.
  • 6 Laboratory for Preventive and Personalized Medicine (MPP Lab), University of Brescia, Brescia, Italy. stefania.mitola@unibs.it.
PMID: 31363885 DOI: 10.1007/s10456-019-09676-y
Abstract

The Bone Morphogenetic Protein 4 (BMP4) regulates multiple biological processes, including vascular development and angiogenesis. Here, we investigated the role of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2/KDR/Flk-1) in mediating the angiogenic activity of BMP4. BMP4 induces a rapid relocation and phosphorylation of VEGFR2/KDR/Flk-1 on the endothelial cell membrane. These effects occur in the absence of a direct interaction of BMP4 and/or BMP receptors with VEGFR2/KDR/Flk-1. At variance, BMP4, by interacting with the BMPRI-II hetero-complex, induces c-Src phosphorylation which, in turn, activates VEGFR2/KDR/Flk-1, leading to an angiogenic response. Accordingly, the BMPR inhibitor dorsomorphin prevents c-Src activation and specific inhibition of c-Src significantly reduces downstream VEGFR2/KDR/Flk-1 phosphorylation and the angiogenic activity exerted by BMP4 in a chick embryo chorioallantoic membrane assay. Together, our data indicate that the pro-angiogenic activity exerted by BMP4 in endothelial cells is mediated by a BMPR-mediated intracellular transactivation of VEGFR2/KDR/Flk-1 via c-Src.

Keywords

Angiogenesis; BMP4; VEGFR2; c-Src.

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