Regulation of extracellular matrix synthesis by mechanical stress

Abstract

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 transduction 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.

Mechanoregulation of gene expression in fibroblasts

“…Mechanoregulation of gene expression has been widely studied in chicken skin fibroblasts, and various mechanisms have been proposed for the mechanoregulation of ECM genes (Chiquet-Ehrismann et al, 1994;Chiquet et al, 1996Chiquet et al, , 2003Chiquet et al, , 2004Sarasa-Renedo and Chiquet, 2005;Sarasa-Renedo et al, in press). The genes of focus in these studies are tenascin-C and collagen fibril-associated type XII collagen.…”

Laser−Micropipet Combination for Single-Cell Analysis

“…33 Forces applied to remove a cell from a surface are transmitted by these adhesion proteins into the cell interior leading to activation of numerous enzymes including tyrosine kinases, serine/threonine kinases, G proteins, proteases, and others. 34,35 Activation of these pathways triggers immediate and long-term changes in cellular physiology. For adherent cells, mechanical manipulation prior to the time of sampling may interfere with measurements of cellular biochemistry.…”

A Neurovascular Blood-Flow Modulation Model via Acupuncture Induced Nitric Oxide

“…The ECM is a multi-component tissue that is able to transduce the internal and external mechanical signals into changes in the tissue structure and function through a process termed mechanochemical transduction [20,21].…”