Nonenzymatic glycation interferes with fibronectin-integrin interactions in vascular smooth muscle cells.
Nonenzymatic glycation interferes with fibronectin-integrin interactions in vascular smooth muscle cells.
复制标题
DOI：
10.1111/micc.12347
复制
发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Hill MA
中科院分区：
文献类型：
--
作者：
Dhar S;Sun Z;Meininger GA;Hill MA
我们的目的是调查是否先进的非酶糖化的细胞外基质（ECM）蛋白，纤连蛋白，影响其正常的整合素介导的相互作用与小动脉血管平滑肌细胞（VSMC）。用原子力显微镜（AFM）观察大鼠提睾肌小动脉VSMC与细胞整合素的相互作用。AFM探针用FN或gFN或用天然或糖化白蛋白（gAlb）功能化作为对照。与天然FN（63.0 ± 1.6%）相比，VSMC与gFN（72.9 ± 3.5%）的粘附概率增加。与天然Alb（40.1 ± 4.7%）相比，VSMC类似地显示出与gAlb粘附的概率增加（63.8 ± 1.7%）。天然FN与VSMC的粘附依赖于α5和β1整合素，而gFN与VSMC的粘附不依赖于整合素。RAGE选择性抑制剂FPS-ZM 1可阻断gFN（和gAlb）粘附，表明糖基化蛋白的粘附是RAGE依赖性的。可溶性gFN不改变FN与VSMC的相互作用，而可溶性天然FN不抑制gFN与VSMC的粘附。相反，gAlb以浓度依赖性方式抑制gFN与VSMC的粘附。FN的糖基化将细胞粘附的性质从整合素依赖性机制转变为RAGE依赖性机制。
We aimed to investigate whether advanced non-enzymatic glycation of the extracellular matrix (ECM) protein, fibronectin, impacts its normal integrin-mediated interaction with arteriolar vascular smooth muscle cells (VSMC). Atomic force microscopy (AFM) was performed on cultured VSMC from rat cremaster arterioles to study native and glycated fibronectin (FN and gFN) interactions with cellular integrins. AFM probes were functionalized with FN or gFN or with native or glycated albumin (gAlb) as controls. VSMC showed increased adhesion probability to gFN (72.9 ± 3.5 %) compared to native FN (63.0 ± 1.6 %). VSMCs similarly showed increased probability of adhesion (63.8 ± 1.7 %) to gAlb compared to native Alb (40.1 ± 4.7 %). Adhesion of native FN to VSMC was α5 and β1 integrin-dependent whereas adhesion of gFN to VSMC was integrin-independent. The RAGE-selective inhibitor, FPS-ZM1, blocked gFN (and gAlb) adhesion suggesting that adhesion of glycated proteins was RAGE-dependent. Interaction of FN with VSMC was not altered by soluble gFN while soluble native FN did not inhibit adhesion of gFN to VSMC. In contrast, gAlb inhibited adhesion of gFN to VSMC in a concentration-dependent manner. Glycation of FN shifts the nature of cellular adhesion from integrin- to RAGE-dependent mechanisms.