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首页> 外文期刊>Matrix biology: Journal of the International Society for Matrix Biology >How do fibroblasts translate mechanical signals into changes in extracellular matrix production?
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How do fibroblasts translate mechanical signals into changes in extracellular matrix production?

机译：成纤维细胞如何将机械信号转化为细胞外基质产生的变化？

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Mechanical forces are important regulators of connective tissue homeostasis. Our recent experiments in vivo indicate that externally applied mechanical load can lead to the rapid and sequential induction of distinct extracellular matrix (ECM) components in fibroblasts, rather than to a generalized hypertrophic response. Thus, ECM composition seems to be adapted specifically to changes in load. Mechanical stress can regulate the production of ECM proteins indirectly, by stimulating the release of a paracrine growth factor, or directly, by triggering an intracellular signalling pathway that activates the gene. We have evidence that tenascin-C is an ECM component directly regulated by mechanical stress: induction of its mRNA in stretched fibroblasts is rapid both in vivo and in vitro, does not depend on prior protein synthesis, and is not mediated by factors released into the medium. Fibroblasts sense force-induced deformations (strains) in their ECM. Findings by other researchers indicate that integrins within cell-matrix adhesions can act as 'strain gauges', triggering MAPK and NF-kappaB pathways in response to changes in mechanical stress. Our results indicate that cytoskeletal 'pre-stress' is important for mechanotransduction to work: relaxation of the cytoskeleton (e.g. by inhibiting Rho-dependent kinase) suppresses induction of the tenascin-C gene by cyclic stretch, and hence desensitizes the fibroblasts to mechanical signals. On the level of the ECM genes, we identified related enhancer sequences that respond to static stretch in both the tenascin-C and the collagen XII promoter. In the case of the tenascin-C gene, different promoter elements might be involved in induction by cyclic stretch. Thus, different mechanical signals seem to regulate distinct ECM genes in complex ways.
机译：机械力是结缔组织动态平衡的重要调节器。我们最近的体内实验表明，外部施加的机械负荷可导致成纤维细胞中不同细胞外基质（ECM）成分的快速顺序诱导，而不是普遍的肥大性反应。因此，ECM组成似乎专门适应了负载的变化。机械应力可以通过刺激旁分泌生长因子的释放来间接调节ECM蛋白的产生，或通过触发激活该基因的细胞内信号通路来直接调节ECM蛋白的产生。我们有证据表明，腱生蛋白-C是直接受机械应力调节的ECM成分：在拉伸的成纤维细胞中，其mRNA的诱导在体内和体外均迅速，不依赖于先前的蛋白质合成，并且不受释放到细胞内的因素的介导。中。成纤维细胞在其ECM中感知力引起的变形（应变）。其他研究人员的发现表明，细胞-基质粘附中的整联蛋白可以充当“应变仪”，响应机械应力的变化而触发MAPK和NF-κB途径。我们的结果表明，细胞骨架的“预应力”对于机械转导起作用很重要：细胞骨架的松弛（例如，通过抑制Rho依赖性激酶）通过循环拉伸抑制了腱生蛋白C基因的诱导，因此使成纤维细胞对机械信号不敏感。在ECM基因的水平上，我们确定了相关的增强子序列，它们在腱生蛋白-C和胶原蛋白XII启动子中均响应静态拉伸。在腱生蛋白C基因的情况下，不同的启动子元件可能参与循环拉伸的诱导。因此，不同的机械信号似乎以复杂的方式调节不同的ECM基因。

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