Dermatopontin Interacts with Fibronectin, Promotes Fibronectin Fibril Formation, and Enhances Cell Adhesion
Dermatopontin Interacts with Fibronectin, Promotes Fibronectin Fibril Formation, and Enhances Cell Adhesion
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DOI：
10.1074/jbc.m110.179762
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发表时间：
2011-04-29
影响因子：
4.8
通讯作者：
Fujiwara, Sakuhei
中科院分区：
文献类型：
--
作者：
Kato, Aiko;Okamoto, Osamu;Fujiwara, Sakuhei
我们报告说，皮桥蛋白（DP）是一种丰富的真皮细胞外基质蛋白，存在于纤维蛋白凝块和伤口液中，它们构成伤口愈合初始阶段的临时基质。血清中也发现了 DP，但浓度低于伤口液中的浓度。 DP 与纤维蛋白和纤连蛋白共定位在纤维蛋白纤维上，并与这两种蛋白质相互作用。 DP 剂量依赖性地增强正常成纤维细胞和 HT1080 细胞对纤维蛋白-纤连蛋白基质的粘附，并且粘附是由 α5β1 整联蛋白介导的。粘附在纤维蛋白-纤连蛋白-DP 复合物上的细胞中的细胞骨架更加组织化。当与 DP 一起孵育时，纤连蛋白形成了纤连蛋白原纤维的不溶性复合物，如通过电子显微镜观察到的。纤连蛋白与 DP 的相互作用位点是第一个、第十三和第十四个 III 型重复序列（III1、III13 和 III14），其中 III13 和 III14 被认为是主要位点。 DP抑制III2-3和III12-14之间的相互作用，而DP特异性且强烈地增强I1-5和III12-14之间的相互作用。由于III2-3和III12-14之间的相互作用涉及纤连蛋白球状构象的形成，而I1-5和III12-14之间的相互作用是形成纤连蛋白原纤维所必需的，因此DP可能通过改变纤连蛋白构象来促进纤连蛋白原纤维的形成。这些结果表明，在伤口愈合的初始阶段，DP对成纤维细胞粘附到临时基质具有加速作用。
We report that dermatopontin (DP), an abundant dermal extracellular matrix protein, is found in the fibrin clot and in the wound fluid, which comprise the provisional matrix at the initial stage of wound healing. DP was also found in the serum but at a lower concentration than that in wound fluid. DP co-localized with both fibrin and fibronectin on fibrin fibers and interacted with both proteins. Both normal fibroblast and HT1080 cell adhesion to the fibrin-fibronectin matrix were dose-dependently enhanced by DP, and the adhesion was mediated by alpha 5 beta 1 integrin. The cytoskeleton was more organized in the cells that adhered to the fibrin-fibronectin-DP complex. When incubated with DP, fibronectin formed an insoluble complex of fibronectin fibrils as visualized by electron microscopy. The interacting sites of fibronectin with DP were the first, thirteenth, and fourteenth type III repeats (III1, III13, and III14), with III13 and III14 assumed to be the major sites. The interaction between III2-3 and III12-14 was inhibited by DP, whereas the interaction between I1-5 and III12-14 was specifically and strongly enhanced by DP. Because the interaction between III2-3 and III12-14 is involved in forming a globular conformation of fibronectin, and that between I1-5 and III12-14 is required for forming fibronectin fibrils, DP promotes fibronectin fibril formation probably by changing the fibronectin conformation. These results suggest that DP has an accelerating role in fibroblast cell adhesion to the provisional matrix in the initial stage of wound healing.