Influence of the extracellular matrix on the regulation of cardiac fibroblast behavior by mechanical stretch
Influence of the extracellular matrix on the regulation of cardiac fibroblast behavior by mechanical stretch
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DOI：
10.1002/jcp.20034
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发表时间：
2004-09-01
影响因子：
5.6
通讯作者：
Carver, W
中科院分区：
文献类型：
--
作者：
Atance, J;Yost, MJ;Carver, W
成纤维细胞在很大程度上负责细胞外基质(ECM)的产生、组织和周转，从而调节心脏的纤维化含量。过度的纤维化与某些形式的血流动力学超负荷有关，如高血压，被认为会导致室腔僵硬增加，并最终导致心力衰竭。因此，机械拉伸在调节成纤维细胞活动中的作用对于我们理解健康和患病的心脏至关重要。然而，对于ECM成分的改变在调节心脏成纤维细胞的机械转导中的作用，人们知之甚少。为了解决这一问题，将大鼠心脏成纤维细胞培养在涂有不同ECM底物的硅橡胶膜上，并循环拉伸不同的时间。实验旨在评估信号通路的激活，以及胶原产生、细胞增殖和形态的变化。丝裂原活化蛋白激酶(MAPK)激活最快，I型胶原蛋白表达最丰富，细胞被随机排列的胶原蛋白和未包被的带电薄膜拉伸。不管ECM底物的性质如何，拉伸的细胞减少了增殖，然而，这种影响在随机组织的胶原上拉伸的细胞中最为明显。最后，细胞在所有ECM底物上拉伸增加了它们的表面积，但这在附着于排列的胶原蛋白、随机排列的胶原蛋白和未涂覆的带电薄膜的细胞中观察到的最明显。综上所述，这些结果表明，心脏成纤维细胞可能根据ECM的组成和组织，在信号转导和特定的长期事件(如基因转录)方面对机械刺激进行不同的解释。(C)2004年Wiley-Liss公司
Fibroblasts are responsible in large part for production, organization, and turnover of the extracellular matrix (ECM), thereby regulating the fibrotic content of the heart. Excessive fibrosis, which has been associated with certain forms of hemodynamic overload such as hypertension, is thought to result in increased ventricular chamber stiffness, and eventual heart failure. As such, the role of mechanical stretch in regulating fibroblast activity is crucial to our understanding of healthy and diseased hearts. However, little is known about the effects of alterations in the composition of the ECM in regulating mechanotransduction in cardiac fibroblasts. In order to address this question, rat cardiac fibroblasts were cultured on silastic membranes coated with different ECM substrates, and cyclically stretched for various durations. Experiments were designed to assess the activation of signaling pathways, as well as changes in collagen production, cellular proliferation, and morphology. Mitogen activated protein kinase (MAP kinase) was most rapidly activated, and collagen I expression was most abundant, in cells stretched on randomly organized collagen, and uncoated charged membranes. Regardless of the nature of the ECM substrate, stretched cells decreased proliferation, however, this effect was most marked in cells stretched on randomly organized collagen. Finally, cells stretched on all ECM substrates increased their surface area, but this was observed most significantly in cells adherent to aligned collagen, randomly organized collagen, and uncoated, charged membranes. Taken together, these results suggest cardiac fibroblasts may differentially interpret a mechanical stimulus, in terms of both signal transduction, and specific long-term events such as gene transcription, based on the composition and organization of the ECM. (C) 2004 Wiley-Liss, Inc.