The relative roles of collagen adhesive receptor DDR2 activation and matrix stiffness on the downregulation of focal adhesion kinase in vascular smooth muscle cells
The relative roles of collagen adhesive receptor DDR2 activation and matrix stiffness on the downregulation of focal adhesion kinase in vascular smooth muscle cells
复制标题
DOI：
10.1016/j.biomaterials.2009.08.036
复制
发表时间：
2009-12-01
期刊：
影响因子：
14
通讯作者：
Plant, Anne L.
中科院分区：
文献类型：
--
作者：
Bhadriraju, Kiran;Chung, Koo-Hyun;Plant, Anne L.
组织内的细胞从其周围的不溶性细胞外基质（ECM）获得机械锚定和特定的分子信号。了解细胞外基质为细胞提供的不同线索的作用对于控制和预测细胞对支架材料的反应至关重要。使用I型胶原的工程细胞外基质，我们研究了胶原基质的硬度、超分子结构和糖基化如何影响细胞FAK的蛋白质水平和肌球蛋白II的激活。我们的研究结果表明：(1)细胞FAK在胶原原纤维上下调，但在非原纤维的胶原单层上没有下调；(2)FAK的下调与胶原原纤维的硬度无关；(3)FAK水平与胶原粘附受体DDR2的酪氨酸磷酸化水平相关。此外，DDR2的siRNA缺失会阻止FAK下调。我们的研究结果表明，胶原受体DDR2参与了粘附在I型胶原基质上的vSMC中FAK水平的调节，并且这些细胞中FAK水平的调节似乎与基质硬度无关。2009爱思唯尔有限公司版权所有。
Cells within tissues derive mechanical anchorage and specific molecular signals from the insoluble extracellular matrix (ECM) that surrounds them. Understanding the role of different cues that extracellular matrices provide cells is critical for controlling and predicting cell response to scaffolding materials. Using an engineered extracellular matrix of Type I collagen we examined how the stiffness, supramolecular structure, and glycosylation of collagen matrices influence the protein levels of cellular FAK and the activation of myosin II. Our results show that (1) cellular FAK is downregulated on collagen fibrils, but not on a non-fibrillar monolayer of collagen, (2) the downregulation of FAK is independent of the stiffness of the collagen fibrils, and (3) FAK levels are correlated with levels of tyrosine phosphorylation of the collagen adhesion receptor DDR2. Further, siRNA depletion of DDR2 blocks FAK downregulation. Our results suggest that the collagen receptor DDR2 is involved in the regulation of FAK levels in vSMC adhered to Type I collagen matrices, and that regulation of FAK levels in these cells appears to be independent of matrix stiffness. (C) 2009 Elsevier Ltd. All rights reserved.