Related Experiment Video
Updated: Jun 10, 2026

Modified In Vivo Matrix Gel Plug Assay for Angiogenesis Studies
Published on: June 30, 2023
Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2
Stefania Mitola1, Cosetta Ravelli, Emanuela Moroni
1Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, Brescia, Italy.
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.
Insights
Gremlin, a bone morphogenic protein antagonist, acts as a novel proangiogenic vascular endothelial growth factor receptor-2 (VEGFR2) agonist. This finding has implications for understanding tumor neovascularization and related diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Developmental Biology
Background:
- Gremlin is a bone morphogenic protein antagonist involved in embryonic development and pathological conditions like cancer.
- Gremlin is a proangiogenic protein within the cystine-knot superfamily, related to TGF-β and VEGFs.
Purpose of the Study:
- To investigate the interaction between gremlin and VEGF receptor-2 (VEGFR2).
- To determine if gremlin can activate VEGFR2 and induce angiogenic responses.
- To explore the implications of gremlin's proangiogenic activity in vascular development and disease.
Main Methods:
- Binding assays to assess gremlin's interaction with VEGFR2.
- Endothelial cell cultures to study VEGFR2 activation by gremlin.
- In vitro and in vivo models to evaluate gremlin-induced angiogenic responses.
Main Results:
- Gremlin binds to VEGFR2 independently of bone morphogenic proteins.
- Gremlin activates VEGFR2 in endothelial cells, similar to VEGF-A.
- Gremlin elicits VEGFR2-dependent angiogenic responses both in vitro and in vivo.
Conclusions:
- Gremlin is a novel proangiogenic VEGFR2 agonist, distinct from VEGF family ligands.
- Gremlin's activity has significant implications for vascular development, angiogenesis-dependent diseases, and tumor neovascularization.
Related Concept Videos
Mechanism of Angiogenesis
Regulation of Angiogenesis and Blood Supply
TGF - β Signaling Pathway
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Mitogens and the Cell Cycle
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...

