Divalent cations (Mg2+, Ca2+) differentially influence the beta 1 integrin-mediated migration of human fibroblasts and keratinocytes to different extracellular matrix proteins.

Divalent cations (Mg2+, Ca2+) differentially influence the beta 1 integrin-mediated migration of human fibroblasts and keratinocytes to different extracellular matrix proteins.
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DOI:
10.1111/j.1600-0625.1995.tb00236.x
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发表时间:
1995-06-01
影响因子:
3.6
通讯作者:
Scharffetter-Kochanek, K
Scharffetter-Kochanek, K
中科院分区:
医学2区
文献类型:
--
作者:
Lange, T S;Kirchberg, J;Scharffetter-Kochanek, K

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角质形成细胞和成纤维细胞的定向迁移是伤口愈合的基本先决条件。整合素的阳离子依赖性亲和力变化负责细胞与细胞外基质蛋白的粘附和去粘附,并参与驱动细胞迁移。已在体外使用Blindwell Boyden室研究了人真皮成纤维细胞和人表皮角质形成细胞向各种细胞外基质蛋白的整合素依赖性迁移中对二价阳离子的具体要求。受试细胞向I型胶原蛋白的迁移由α 2 β 1整联蛋白介导,向纤连蛋白的迁移由α 3 β 1和α 5 β 1整联蛋白的联合作用介导,成纤维细胞向层粘连蛋白的迁移依赖于α 2 β 1和α 6 β 1整联蛋白。未检测到角质形成细胞向层粘连蛋白的迁移。Mg 2+单独诱导细胞迁移,最佳浓度为2 mM的成纤维细胞和10 mM的角质形成细胞。2 mM的单独Ca 2+仅略微增强成纤维细胞和角质形成细胞迁移。在较高浓度下,Ca ~(2+)抑制Mg ~(2+)的刺激作用。2 mM Ca 2+与2 mM Mg 2+组合显示出对成纤维细胞向纤连蛋白迁移的附加刺激作用。这些数据表明,细胞外二价阳离子差异影响整合素介导的细胞迁移。Mg 2 +/Ca 2+的浓度梯度,如在组织损伤中所报道的,因此可能在组织重塑所需的细胞迁移中起调节作用。
Directed migration of keratinocytes and fibroblasts is a fundamental prerequisite in wound healing. Cation-dependent affinity changes of integrins are responsible for cell adhesion to and deadhesion from extracellular matrix proteins and have been implicated in driving cell migration. The specific requirements for divalent cations in the integrin-dependent migration of human dermal fibroblasts and human epidermal keratinocytes to various extracellular matrix proteins have been studied in vitro using blindwell Boyden chambers. The migration of the tested cells to collagen type I was mediated by the alpha 2 beta 1 integrins, to fibronectin by the combined action of the alpha 3 beta 1 and the alpha 5 beta 1 integrin, and the migration of fibroblasts to laminin dependent both on the alpha 2 beta 1 and the alpha 6 beta 1 integrins. No migration of keratinocytes to laminin was detected. Mg2+ alone induced cell migration with an optimum at 2 mM for fibroblasts and at 10 mM for keratinocytes. Ca2+ alone at 2 mM only marginally enhanced fibroblast and keratinocyte migration. At higher concentrations Ca2+ suppressed the stimulatory Mg2+ effect. 2 mM Ca2+ combined with 2 mM Mg2+ showed an additive stimulatory effect on the migration of fibroblasts to fibronectin. These data suggest that extracellular divalent cations differentially influence the integrin-mediated cell migration. A concentration gradient of Mg2+/Ca2+, as reported in tissue injury, thus may play a regulatory role in cell migration required for tissue remodelling.