Suppression of cell adhesion through specific integrin crosstalk on mixed peptide-polysaccharide matrices
Suppression of cell adhesion through specific integrin crosstalk on mixed peptide-polysaccharide matrices
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DOI：
10.1016/j.biomaterials.2014.10.005
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发表时间：
2015-01-01
期刊：
影响因子：
14
通讯作者：
Nomizu, Motoyoshi
中科院分区：
文献类型：
--
作者：
Hozumi, Kentaro;Fujimori, Chikara;Nomizu, Motoyoshi
不同整合素的串扰与不同类型的细胞外基质蛋白结合，促进特定功能。这种串扰尚未得到深入研究。之前，我们证明整合素-多聚糖串扰可加速细胞粘附。在这里，我们使用混合肽-多糖（壳聚糖或藻酸盐）基质评估了两种不同整合素的串扰。将两种不同的整合素结合肽 FIB1（整合素 α v β 3）、EF1zz（整合素 α 2 β 1）和 531（整合素 α 3 β 1）以不同摩尔比（9:1、4:1、1:1）混合并缀合在多糖基质上。 FIB1/EF1zz-和FIB1/531-多糖基质的混合物在人真皮成纤维细胞(HDF)与单多糖基质的粘附方面没有表现出任何差异。有趣的是，EF1zz/531-多糖基质（摩尔比= 1:4）表现出细胞粘附显着降低，但其他EF1zz/531-多糖基质没有表现出任何差异。当我们检查EF1zz/531(1:4)的信号转导时，FAK的Y397磷酸化显着降低，但Src的Y514磷酸化没有表现出任何差异。进一步的研究表明，这种抑制是由 PI3K 信号通过整合素的激活介导的，而 PKA 信号则调节 HDF 附着的抑制。这些发现表明，使用受体特异性配体的混合肽-多糖基质可以通过受体特异性串扰调节细胞功能，并且是理解受体特异性串扰的有用方法。 (C) 2014 Elsevier Ltd. 保留所有权利。
Crosstalk of different integrins, which bind to distinct types of extracellular matrix proteins, promotes specific functions. This crosstalk has not been investigated in depth. Previously, we demonstrated that integrin-syndecan crosstalk accelerated cell adhesion. Here, we evaluated the crosstalk of two different integrins using mixed peptide-polysaccharide (chitosan or alginate) matrices. Two different integrin binding peptides, FIB1 (integrin alpha v beta 3), EF1zz (integrin alpha 2 beta 1), and 531 (integrin alpha 3 beta 1), were mixed in various molar ratios (9:1, 4:1, 1:1) and conjugated on a polysaccharide matrix. The mixture of FIB1/EF1zz- and FIB1/531-polysaccharide matrices did not show any difference in human dermal fibroblast (HDF) adhesion against the mono polysaccharide matrices. Interestingly, the EF1zz/531-polysaccharide matrix (molar ratio = 1:4) exhibited significantly decreased cell adhesion, but other EF1zz/531-polysaccharide matrices did not show any difference. When we examined the signal transduction of the EF1zz/531(1:4), Y397 phosphorylation of FAK significantly decreased but Y514 phosphorylation of Src did not exhibit any differences. Further investigation revealed that this suppression was mediated by PI3K signaling through the activation of integrin, and PKA signaling modulated suppression of HDF attachment. These findings suggest that a mixed peptide-polysaccharide matrix using receptor specific ligands can regulate cellular functions through receptor-specific crosstalk and is a useful approach to understand receptor specific crosstalk. (C) 2014 Elsevier Ltd. All rights reserved.