Regulation of extracellular matrix synthesis by mechanical stress
Regulation of extracellular matrix synthesis by mechanical stress
复制标题
DOI：
10.1139/o96-080
复制
发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
ChiquetEhrismann, R
中科院分区：
文献类型：
--
作者：
Chiquet, M;Matthisson, M;ChiquetEhrismann, R
细胞外基质（ECM）为组织提供机械支持，是细胞粘附和分化的基质。细胞通过特定的细胞表面受体如整合素与ECM结合。当与ECM配体结合时，这些受体可以激活细胞内的信号转导途径，并可以充当机械化学换能器。因此，细胞与ECM的相互作用可以调节基因表达，尽管确切的机制尚不清楚。在部分由细胞-ECM相互作用控制的基因中，是某些ECM组分本身的基因。例如，骨细胞重塑其基质并重新定向骨小梁以响应机械应变。最近，我们发现附着在紧张的胶原基质上的成纤维细胞比松弛基质中的细胞产生更多的ECM糖蛋白腱生蛋白和胶原XII。在体内，这两种蛋白质在机械应变高的地方特异性表达。我们还发现，鸡腱生蛋白基因启动子包含一个新的顺式作用，“应变响应”的元素，导致在细胞附着到应变胶原基质增强转录。类似的增强子元件可能存在于机械应力诱导的其他基因的启动子中。可以推测，结缔组织细胞在其ECM环境中感知力载体，并通过调节特定ECM基因的转录对改变的机械需求做出反应;该过程是基质重塑的先决条件。
The extracellular matrix (ECM) provides mechanical support to tissues and is a substrate for cell adhesion and differentiation. Cells bind to ECM via specific cell surface receptors such as integrins. When engaging with ECM ligands, these receptors can activate signal tranduction pathways within the cells and may act as mechanochemical transducers. Thus, interaction of cells with ECM can modulate gene expression although the exact mechanisms are not known. Among the genes that are, in part, controlled by cell-ECM interactions are those for certain ECM components themselves. Bone cells, for example, remodel their matrix and reorient bone trabeculae in response to mechanical strain. Recently, we found that fibroblasts attached to a strained collagen matrix produce more of the ECM glycoproteins tenascin and collagen XII than cells in a relaxed matrix. In vivo, these two proteins are specifically expressed in places where mechanical strain is high. We also showed that the chick tenascin gene promoter contains a novel cis-acting, ''strain-responsive'' element that causes enhanced transcription in cells attached to a strained collagen matrix. Similar enhancer elements might be present in the promoters of other genes induced by mechanical stress. It can be speculated that connective tissue cells sense force vectors in their ECM environment and react to altered mechanical needs by regulating the transcription of specific ECM genes; this process is a prerequisite for matrix remodeling.