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Sushi repeat protein X‐linked 2, a novel mediator of angiogenesis
Author(s) -
Miljkovic-Licina Marijana,
Hammel Philippe,
Garrido-Urbani Sarah,
BradAed Paul F.,
Szepetowski Pierre,
Imhof Beat A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-135202
Subject(s) - angiogenesis , immunostaining , gene silencing , mediator , endothelial stem cell , microbiology and biotechnology , biology , in situ hybridization , endothelium , small interfering rna , neovascularization , urokinase receptor , cell , cancer research , cell culture , messenger rna , immunology , transfection , gene , immunohistochemistry , genetics , in vitro
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 endothe‐lial 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.—Miljkovic‐Licina, M., Hammel, P., Garrido‐Urbani, S., Bradfield, P. F., Szepetowski, P., Imhof, B. A. Sushi repeat protein X‐linked 2, a novel mediator, of angiogenesis. FASEBJ. 23, 4105‐4116 (2009). www.fasebj.org