The mesenchymal α11β1 integrin attenuates PDGF-BB-stimulated chemotaxis of embryonic fibroblasts on collagens
The mesenchymal α11β1 integrin attenuates PDGF-BB-stimulated chemotaxis of embryonic fibroblasts on collagens
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DOI：
10.1016/j.ydbio.2004.03.006
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发表时间：
2004-06-15
影响因子：
2.7
通讯作者：
Gullberg, D
中科院分区：
文献类型：
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作者：
Popova, SN;Rodriguez-Sánchez, B;Gullberg, D
α 11 β 1构成整联蛋白家族的最新成员，并且已经显示出对间充质组织中发现的间质胶原的结合偏好。我们先前已经观察到，当α 11 β 1整合素在缺乏内源性胶原受体的细胞中表达时，它可以在体外介导PDGF-BB依赖的对胶原1的趋化性。为了确定PDGF和α 11 β 1在体内哪些细胞中可能协同调节细胞迁移，我们详细研究了α 11整合素链在小鼠胚胎中的表达和分布，并测试了PDGF异构体刺激α 11 β 1介导的胚胎成纤维细胞迁移的能力。在胚胎小鼠头部，alpha 11蛋白和RNA定位于外胚间充质来源的细胞。在牙周膜中，α 11作为唯一可检测的胶原结合整合素表达，因此α 11 β 1是该细胞群中细胞迁移和基质组织的主要受体。在胚胎的其余部分中，α 11链在间充质细胞亚群中表达，包括肌腱/韧带成纤维细胞、软骨膜细胞和肠绒毛成纤维细胞。大多数表达α 11的细胞也表达α 2整联蛋白链，但没有发现与α 1整联蛋白链的可检测的重叠。在表达多种胶原受体的细胞中，这些可能起到促进更稳定的细胞粘附的作用，并使细胞对趋化性刺激更具抗性。野生型胚胎成纤维细胞主要激活PDGF β受体以响应PDGF-BB，并在体外响应PDGF-BB在胶原I、II、III、IV、V和XI上迁移，而在胶原受体库中缺乏α 11 β 1的突变成纤维细胞在用PDGF-BB刺激时对胶原表现出更强的趋化反应。在胚胎成纤维细胞的细胞背景下，α 11 β 1，因此antimigration.We推测，PDGF BB依赖的细胞迁移的间充质细胞的胶原蛋白受体库，和干扰这一库可能会导致不受管制的细胞迁移，可能会影响正常的胚胎发育和组织结构。(C)2004爱思唯尔公司All rights reserved.
alpha11beta1 constitutes the most recent addition to the integrin family and has been shown to display a binding preference for interstitial collagens found in mesenchymal tissues. We have previously observed that when alpha11beta1 integrin is expressed in cells lacking endogenous collagen receptors, it can mediate PDGF-BB-dependent chemotaxis on collagen 1 in vitro. To determine in which cells PDGF and alpha11beta1 might cooperate in regulating cell migration in vivo, we studied in detail the expression and distribution of alpha11 integrin chain in mouse embryos and tested the ability of PDGF isoforms to stimulate the a11beta1-mediated cell migration of embryonic fibroblasts.Full-length mouse alpha11 cDNA was sequenced and antibodies were raised to deduced alpha11 integrin amino acid sequence. In the embryonic mouse head, alpha11 protein and RNA were localized to ectomesenchymally derived cells. In the periodontal ligament, alpha11 was expressed as the only detectable collagen-binding integrin, and alpha11beta1 is thus a major receptor for cell migration and matrix organization in this cell population. In the remainder of the embryo, the alpha11 chain was expressed in a subset of mesenchymal cells including tendon/ligainent fibroblasts, perichondrial cells, and intestinal villi fibroblasts. Most of the alpha11-expressing cells also expressed the alpha2 integrin chain, but no detectable overlap was found with the alpha1 integrin chain. In cells expressing multiple collagen receptors, these might function to promote a more stable cell adhesion and render the cells more resistant to chemotactic stimuli.Wild-type embryonic fibroblasts activated mainly the PDGF beta receptor in response to PDGF-BB and migrated on collagens I, II, III, IV, V and XI in response to PDGF-BB in vitro, whereas mutant fibroblasts that lacked alpha11beta1 in their collagen receptor repertoire showed a stronger chemotactic response on collagens when stimulated with PDGF-BB. In the cellular context of embryonic fibroblasts, alpha11beta1 is thus antimigratory.We speculate that the PDGF BB-dependent cell migration of mesenchymal cells is tightly regulated by the collagen receptor repertoire, and disturbances of this repertoire might lead to unregulated cell migration that could affect normal embryonic development and tissue structure. (C) 2004 Elsevier Inc. All rights reserved.