Gremlin is a novel agonist of the major pro-angiogenic receptor VEGFR2.
Blood 2010 Jul 21; In press
Mitola S, Ravelli C, Moroni E, Salvi V, Leali D, Ballmer-Hofer K, Zammataro L, Presta M
Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy;
The bone morphogenic protein (BMP) antagonist gremlin is expressed during embryonic development and under different pathological conditions, including cancer. Gremlin is a pro-angiogenic protein belonging to the cystine-knot superfamily that includes transforming growth factor-beta proteins and the angiogenic vascular endothelial growth factors (VEGFs). Here, we demonstrate that gremlin binds VEGF receptor-2 (VEGFR2), the main transducer of VEGF-mediated angiogenic signals, in a BMP-independent manner. Similar to VEGF-A, gremlin activates VEGFR2 in endothelial cells, leading to VEGFR2-dependent angiogenic responses in vitro and in vivo. Gremlin thus represents a novel pro-angiogenic VEGFR2 agonist distinct from the VEGF family ligands with implications in vascular development, angiogenesis-dependent diseases, and tumor neovascularization.
Keywords: Gremlin VEGFR2 angiogenic