Dermatopontin regulates fibrin formation and its biological activity
Dermatopontin regulates fibrin formation and its biological activity
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皮桥蛋白调节纤维蛋白形成及其生物活性
DOI：
10.1038/jid.2013.305
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Fujiwara S.
中科院分区：
文献类型：
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作者：
Wu W;Okamoto O;Kato A;Matsuo N;Nomizu M;Yoshioka H;Fujiwara S.
皮桥蛋白 (DP) 是真皮中的一种小的细胞外基质成分。纤维蛋白是受伤后形成的临时基质的主要成分。之前，我们发现DP存在于临时基质中，并且它与纤维蛋白相互作用。在这里，我们研究了 DP 对纤维蛋白功能的作用。 DP与纤维蛋白单体和原纤维相互作用，并在纤维蛋白形成过程中并入原纤维中。 DP序列PHGQVVVAVRS被鉴定为纤维蛋白结合位点，纤维蛋白的球状D结构域是DP的结合位点。 DP 加速纤维蛋白原纤维形成结构修饰的原纤维。 DP 存在下形成的纤维蛋白原纤维增强了内皮细胞附着和细胞扩散。与仅附着在纤维蛋白原纤维上的细胞相比，附着的细胞形成了更有组织的细胞骨架。细胞粘附的主要受体被确定为αvβ3整合素，协同受体是含有β1的整合素种类，可能是α5β1整合素。这些结果表明DP可以改变纤维蛋白的某些生物学功能，从而揭示了这种细胞外基质蛋白的另一个功能。此外，纤维蛋白-DP 复合物可能有助于开发改进的人工基质，以改善伤口愈合。
Dermatopontin (DP) is a small extracellular matrix component in the dermis. Fibrin is a major component of a provisional matrix that is formed just after wounding. Previously, we found that DP was present in the provisional matrix, and it interacted with fibrin. Here, we examined the role of DP on fibrin function. DP interacted with both the fibrin monomer and fibrils, and was incorporated into the fibrils during fibrin formation. A DP sequence, PHGQVVVAVRS, was identified as a fibrin-binding site, and a globular D domain of fibrin was the binding site for DP. DP accelerated fibrin fibril formation into structurally modified fibrils. Fibrin fibrils formed in the presence of DP enhanced both endothelial cell attachment and cell spreading. The attached cells developed a more organized cytoskeleton when compared with those that attached to fibrin fibrils only. The main receptor for cell adhesion was identified as αvβ3 integrin, and a cooperating receptor was a β1-containing integrin species, probably α5β1 integrin. These results indicate that DP can modify certain biological functions of fibrin, and thus a another function of this extracellular matrix protein was revealed. In addition, the fibrin–DP complex might become useful for developing an improved artificial matrix for improving wound healing.