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PMID:19667118

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Citation

Miljkovic-Licina, M, Hammel, P, Garrido-Urbani, S, Bradfield, PF, Szepetowski, P and Imhof, BA (2009) Sushi repeat protein X-linked 2, a novel mediator of angiogenesis. FASEB J. 23:4105-16

Abstract

On appropriate stimuli, quiescent endothelial cells start to proliferate and form de novo blood vessels through angiogenesis. To further define molecular mechanisms accompanying the activation of endothelial cells during angiogenesis, we identified genes that were differentially regulated during this process using microarray analyses. In this work, we established a regulatory role for Sushi repeat protein X-linked 2 (Srpx2) in endothelial cell remodeling during angiogenesis. In particular, silencing of Srpx2 using small interfering RNAs (siRNAs) specifically attenuated endothelial cell migration and delayed angiogenic sprout formation. In vivo, Srpx2 expression was detected in de novo formation of blood vessels in angiogenic tissues by in situ mRNA hybridization and immunostaining. Pulldown experiments identified Srpx2 as a ligand for vascular uPAR, a key molecule involved in invasive migration of angiogenic endothelium. Immunostaining revealed coexpression of the Srpx2 and uPAR on vascular endothelium. These findings suggest that Srpx2 regulates endothelial cell migration and tube formation and provides a new target for modulating angiogenesis.

Links

PubMed Online version:10.1096/fj.09-135202

Keywords

Endothelial Cells/metabolism; Gene Expression Profiling; Gene Expression Regulation/physiology; Gene Silencing; Humans; Neovascularization, Physiologic/physiology; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Protein Array Analysis; Receptors, Urokinase Plasminogen Activator/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:UPAR

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8R054

F

Seeded From UniProt

complete

MOUSE:SRPX2

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35456

F

Seeded From UniProt

complete

MOUSE:SRPX2

involved_in

GO:0090050: positive regulation of cell migration involved in sprouting angiogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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