Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of α2β1 integrin activity
Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of α2β1 integrin activity
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DOI：
10.1074/jbc.m710025200
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发表时间：
2008-06-20
影响因子：
4.8
通讯作者：
Eble, Johannes A.
中科院分区：
文献类型：
--
作者：
Fiedler, Lorna R.;Schoenherr, Elke;Eble, Johannes A.
蛋白聚糖核心蛋白聚糖由萌芽的内皮细胞表达，但不由静止的内皮细胞表达，如果没有蛋白聚糖，血管生成就会失调。此前，我们已经证明核心蛋白聚糖核心蛋白可以结合并激活内皮细胞中的胰岛素样生长因子-I 受体（IGF-IR）。在这项研究中，我们发现核心蛋白聚糖可促进 α2β1 整合素依赖性内皮细胞在 I 型纤维胶原上的粘附和迁移。我们提供的证据表明，核心蛋白聚糖通过激活 IGF-IR 和小 GTPase Rac 刺激细胞骨架和粘着斑重组，从而调节细胞-基质相互作用。此外，核心蛋白聚糖的糖胺聚糖部分在不同于I型胶原蛋白结合A结构域的位点与α2β1而不是α1β1整联蛋白相互作用，以变构调节整联蛋白的I型胶原蛋白结合活性。我们提出，与静止的内皮细胞相比，在血管生成中诱导核心蛋白聚糖表达可通过 IGF-IR 信号传导和影响 α2β1 整联蛋白活性，在富含间质胶原 I 的环境中促进运动表型。
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 alpha 2 beta 1 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 alpha 2 beta 1, but not alpha 1 beta 1 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 alpha 2 beta 1 integrin activity.