Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2
- Mitola, Stefania Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy;
- Ravelli, Cosetta Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy;
- Moroni, Emanuela Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy;
- Salvi, Valentina Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy;
- Leali, Daria Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy;
- Ballmer-Hofer, Kurt Paul Scherrer Institut, Biomolecular Research, Villigen PSI, Switzerland; and
- Zammataro, Luca University of Milan, Istituto Clinico Humanitas Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, Milan, Italy
- Presta, Marco Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy;
Published in:
- Blood. - American Society of Hematology. - 2010, vol. 116, no. 18, p. 3677-3680
English
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.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1182/blood-2010-06-291930
- ISSN 0006-4971
- Persistent URL
- https://sonar.ch/global/documents/139694
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