Decorin Regulates Endothelial Cell Motility on Collagen I through Activation of Insulin-like Growth Factor I Receptor and Modulation of α2β1 Integrin Activity

• Published in: The Journal of biological chemistry Vol. 283; no. 25; p. 17406
• Main Authors: Lorna R. Fiedler, Elke Schönherr, Rachel Waddington, Stephan Niland, Daniela G. Seidler, Daniel Aeschlimann, Johannes A. Eble
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 20-06-2008
• DOI: 10.1074/jbc.M710025200
• EISSN: 1083-351X
• ISSN: 0021-9258

The proteoglycan decorin is expressed by sprouting but not quiescent endothelial cells, and angiogenesis is dysregulated in
its absence. Previously, we have shown that decorin core protein can bind to and activate insulin-like growth factor-I receptor
(IGF-IR) in endothelial cells. In this study, we show that decorin promotes α2β1 integrin-dependent endothelial cell adhesion
and migration on fibrillar collagen type I. We provide evidence that decorin modulates cell-matrix interaction in this context
by stimulating cytoskeletal and focal adhesion reorganization through activation of the IGF-IR and the small GTPase Rac. Further,
the glycosaminoglycan moiety of decorin interacts with α2β1, but not α1β1 integrin, at a site distinct from the collagen I-binding
A-domain, to allosterically modulate collagen I-binding activity of the integrin. We propose that induction of decorin expression
in angiogenic, as opposed to quiescent, endothelial cells promotes a motile phenotype in an interstitial collagen I-rich environment
by both signaling through IGF-IR and influencing α2β1 integrin activity.