The role of ERK signaling in protein hydrogel remodeling by vascular smooth muscle cells
The role of ERK signaling in protein hydrogel remodeling by vascular smooth muscle cells
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DOI：
10.1016/j.biomaterials.2007.05.007
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发表时间：
2007-09-01
期刊：
影响因子：
14
通讯作者：
Stegemann, Jan P.
中科院分区：
文献类型：
--
作者：
Hong, Helen;McCullough, Caltlyn M.;Stegemann, Jan P.
I型胶原蛋白和纤维蛋白水凝胶已用于基于细胞的疗法和组织工程。这些基质可以被细胞分解和重塑，但这些蛋白质对细胞功能的影响尚未完全了解。我们研究了血管平滑肌细胞（VSMC）对I型胶原、纤维蛋白或这些蛋白质的1：1复合混合物的2D和3D基质的细胞外信号调节激酶（ERK）信号通路的激活。培养3天后，ERK磷酸化、骨桥蛋白分泌和MMP-2活化均在3D基质中显著增加，与2D基质相比。合成表型和磷酸化ERK水平的这些蛋白质标志物之间存在强的正相关性，并且这种关系在基质几何形状和组成中持续存在。细胞增殖在3D矩阵呈负相关ERK激活，而在2D基板上观察到适度的正相关。ERK信号传导的药理学抑制证实该途径参与了观察到的表型变化。这项研究表明，上下文激活的ERK通路的结果在不同的影响细胞表型，这取决于几何形状和ECM的组成。这些发现增加了我们对蛋白质基水凝胶生物材料中细胞功能和重塑的理解。(c)2007爱思唯尔有限公司保留所有权利。
Collagen type I and fibrin hydrogels have been used for cell-based therapies and tissue engineering. These matrices can be broken down and remodeled by cells, but the effects that these proteins have on cell function are not completely understood. We examined activation of the extracellular signal-regulated kinase (ERK) signaling pathway by vascular smooth muscle cells (VSMC) in response to 2D and 3D matrices of type I collagen, fibrin, or a 1: 1 composite mixture of these proteins. After 3 days of culture, ERK phosphorylation, osteopontin secretion, and MMP-2 activation were all markedly increased in 3D matrices, compared with 2D substrates. A strong positive correlation existed between these protein markers of the synthetic phenotype and phosphorylated ERK levels, and this relationship persisted across matrix geometries and compositions. Cell proliferation in 3D matrices was inversely correlated to ERK activation, while on 2D substrates a modest positive correlation was observed. Pharmacologic inhibition of ERK signaling confirmed that this pathway was involved in the observed phenotype shifts. This study suggests that contextual activation of the ERK pathway results in different effects on cell phenotype, depending on the geometry and composition of the ECM. These findings add to our understanding of cell function and remodeling in protein-based hydrogel biomaterials.(c) 2007 Elsevier Ltd. All rights reserved.