RGD Reference Report - Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor. - Rat Genome Database

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Bone morphogenic protein antagonist Drm/gremlin is a novel proangiogenic factor.

Authors: Stabile, H  Mitola, S  Moroni, E  Belleri, M  Nicoli, S  Coltrini, D  Peri, F  Pessi, A  Orsatti, L  Talamo, F  Castronovo, V  Waltregny, D  Cotelli, F  Ribatti, D  Presta, M 
Citation: Stabile H, etal., Blood. 2007 Mar 1;109(5):1834-40. Epub 2006 Oct 31.
RGD ID: 8553524
Pubmed: PMID:17077323   (View Abstract at PubMed)
DOI: DOI:10.1182/blood-2006-06-032276   (Journal Full-text)

Angiogenesis plays a key role in various physiologic and pathologic conditions, including tumor growth. Drm/gremlin, a member the Dan family of bone morphogenic protein (BMP) antagonists, is commonly thought to affect different processes during growth, differentiation, and development by heterodimerizing various BMPs. Here, we identify Drm/gremlin as a novel proangiogenic factor expressed by endothelium. Indeed, Drm/gremlin was purified to homogeneity from the conditioned medium of transformed endothelial cells using an endothelial-cell sprouting assay to follow protein isolation. Accordingly, recombinant Drm/gremlin stimulates endothelial-cell migration and invasion in fibrin and collagen gels, binds with high affinity to various endothelial cell types, and triggers tyrosine phosphorylation of intracellular signaling proteins. Also, Drm/gremlin induces neovascularization in the chick embryo chorioallantoic membrane. BMP4 does not affect Drm/gremlin interaction with endothelium, and both molecules exert a proangiogenic activity in vitro and in vivo when administered alone or in combination. Finally, Drm/gremlin is produced by the stroma of human tumor xenografts in nude mice, and it is highly expressed in endothelial cells of human lung tumor vasculature when compared with non-neoplastic lung. Our observations point to a novel, previously unrecognized capacity of Drm/gremlin to interact directly with target endothelial cells and to modulate angiogenesis.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Grem1Ratpositive regulation of angiogenesis involved_inIMP PMID:17077323BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Grem1  (gremlin 1, DAN family BMP antagonist)


Additional Information