BMP6/TAZ-Hippo signaling modulates angiogenesis and endothelial cell response to VEGF

• DOI: 10.1007/s10456-020-09748-4
• Publication Date: 2020-10-06T14:02:41Z
• Authors: H. H. Pulkkinen; M. Kiema; J. P. Lappalainen; A. Toropainen; M. Beter; A. Tirronen; L. Holappa; H. Niskanen; M. U. Kaikkonen; S. Ylä-Herttuala; Johanna P. Laakkonen
• Keywords: Hippo signaling pathway

Abstract The BMP/TGFβ-Smad, Notch and VEGF signaling guides formation of endothelial tip stalk cells. However, the crosstalk bone morphogenetic proteins (BMPs) vascular growth factor receptor 2 (VEGFR2) has remained largely unknown. We demonstrate that BMP family members regulate VEGFR2 signaling, act via TAZ-Hippo pathway. BMPs were found to be regulated after gene transfer in C57/Bl6 mice a porcine myocardial ischemia model. 2/4/6 identified as endothelium-specific targets VEGF. BMP2 modulated VEGF-mediated sprouting Delta like Canonical Ligand 4 (DLL4). BMP6 by regulating expression acted Hippo effector TAZ, known cell survival/proliferation, dysregulated cancer. In matrigel plug assay nude was further demonstrated induce angiogenesis. is first member directly both neovessel formation. It may thus serve target pro/anti-angiogenic therapies.