Mechanoregulation of gene expression in fibroblasts

Abstract

Mechanical loads placed on connective tissues alter gene expression in fibroblasts through mechanotransduction mechanisms by which cells convert mechanical signals into cellular biological events, such as gene expression of extracellular matrix components (e.g., collagen). This mechanical regulation of ECM gene expression affords maintenance of connective tissue homeostasis. However, mechanical loads can also interfere with homeostatic cellular gene expression and consequently cause the pathogenesis of connective tissue diseases such as tendinopathy and osteoarthritis. Therefore, the regulation of gene expression by mechanical loads is closely related to connective tissue physiology and pathology. This article reviews the effects of various mechanical loading conditions on gene regulation in fibroblasts and discusses several mechanotransduction mechanisms. Future research directions in mechanoregulation of gene expression are also suggested.

3D collagen cultures under well‐defined dynamic strain: A novel strain device with a porous elastomeric support

“…Because flow and strain are necessarily coupled, we could not differentiate specific responses to flow versus strain, but this alignment was consistent with our previous studies showing that fibroblasts in collagen gels undergoing interstitial flow alone (without matrix compression) align perpendicular to the direction of flow Swartz, 2003, 2006). We note that most of the previous work on fibroblast mechanobiology has been done by applying either tension or confined compression to the cells (Eastwood et al, 1998;Grinnell, 2003;Liu et al, 1999b;Wang et al, 2007), with tensional forces driving alignment of cells parallel to the strain direction (Henshaw et al, 2006;Voge et al, 2008); this is consistent with our findings. This demonstrates the usefulness of this model system for mechanobiology involving 3D dynamic compressive or tensile stresses.…”

Increased TGF-β: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

“…Because the aforementioned results were compatible with enhanced TGF-␤ signaling after stretching of fetal lungs by TO, pulmonary expression of typical TGF-␤ downstream targets was evaluated in the rabbit model at transcriptional and posttranslational levels. Extracellular matrix synthesis, which increases in vitro under mechanical load (65), is a hallmark of TGF-␤ activation (46). Herein, fibronectin as well as collagens I and III were preferentially evaluated since they colocalize with TGF-␤ during lung morphogenesis (25).…”

“…The three TGF-␤ isoforms are secreted as latent complexes bound to the extracellular matrix. Latent complexes release mature TGF-␤ upon proteolytic cleavage by matrix metalloproteinases (33), acidification (34), mechanical stretch (65), or conformational changes induced by thrombospondin-1 (5). Following binding of mature forms to TGF-␤ type I and II receptors, signal transduction is initiated through Smad-dependent or -independent routes that modify transcription of genes controlling extracellular matrix homeostasis and various cell functions (5).…”

TheC. elegansUNC-23 protein, a member of the BCL-2-associated athanogene (BAG) family of chaperone regulators, interacts with HSP-1 to regulate cell attachment and maintain hypodermal integrity

“…4 Cells are able to control the deposition, composition and maintenance of molecules that make up their surrounding extracellular matrix (ECM), based on the type and magnitude of the mechanical stresses that act on the tissue. 5 Cells under mechanical stress have also been shown to respond by changing the distribution of the structural components that associate with the cytoskeleton and anchoring junctions. 6 The compositions of the biopolymers (i.e.…”