title: Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of alpha2beta1 integrin activity.
abstract: 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 alpha2beta1 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 alpha2beta1, but not alpha1beta1 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 alpha2beta1 integrin activity.
authors.affiliation: Matrix Biology and Tissue Repair Research Unit, School of Dentistry, Cardiff University, Heath Park, Cardiff, United Kingdom CF14 4XY. fiedlerlr@cardiff.ac.uk
authors.forename: Lorna R
authors.initials: LR
authors.lastname: Fiedler
authors.forename: Elke
authors.initials: E
authors.lastname: Schönherr
authors.forename: Rachel
authors.initials: R
authors.lastname: Waddington
authors.forename: Stephan
authors.initials: S
authors.lastname: Niland
authors.forename: Daniela G
authors.initials: DG
authors.lastname: Seidler
authors.forename: Daniel
authors.initials: D
authors.lastname: Aeschlimann
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Eble
mesh_terms: D000495:Allosteric Site; D002465:Cell Movement; D024042:Collagen Type I / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D058575:Decorin; D042783:Endothelial Cells / Q000166:cytology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D011509:Proteoglycans / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D038982:Integrin alpha2beta1; D011509:Proteoglycans; D007334:Insulin-Like Growth Factor I; D051416:Focal Adhesion Protein-Tyrosine Kinases