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. 2010 Nov 4;116(18):3677-80.
doi: 10.1182/blood-2010-06-291930. Epub 2010 Jul 21.

Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2

Stefania Mitola  1 , Cosetta Ravelli, Emanuela Moroni, Valentina Salvi, Daria Leali, Kurt Ballmer-Hofer, Luca Zammataro, Marco Presta
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Free article

Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2

Stefania Mitola et al. Blood. .
Free article

Abstract

The bone morphogenic protein antagonist gremlin is expressed during embryonic development and under different pathologic conditions, including cancer. Gremlin is a proangiogenic protein belonging to the cystine-knot superfamily that includes transforming growth factor-β 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 bone morphogenic protein-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 proangiogenic VEGFR2 agonist distinct from the VEGF family ligands with implications in vascular development, angiogenesis-dependent diseases, and tumor neovascularization.

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