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Review
. 2007 Apr 15;391(1-2):1-15.
doi: 10.1016/j.gene.2007.01.014. Epub 2007 Jan 31.

Mechanoregulation of gene expression in fibroblasts

James H-C Wang  1 , Bhavani P Thampatty, Jeen-Shang Lin, Hee-Jeong Im
Affiliations
Review

Mechanoregulation of gene expression in fibroblasts

James H-C Wang et al. Gene. .

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.

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Figures

Fig. 1
Fig. 1
An illustration of 2-D in vitro models for studying mechanobiological responses of fibroblasts. A. Uniaxial stretching. B. Biaxial stretching. When two stretches (εx and εy) are equal, it is referred to as equibiaxial stretching.
Fig. 2
Fig. 2
Shown is the fibroblast-populated collagen gel (FPCG). This type of 3-D in vitro model has been used to study the effects of internal mechanical gel tension on fibroblasts. Also, an external mechanical stretching can be applied to the gel in this model. Note that the fibroblasts in the gel generate tension, and as a result, the gel changes from rectangular (arrow) to parabolic shape (triangle).
Fig. 3
Fig. 3
A conceptual illustration of several cellular mechanotransduction mechanisms. Mechanical loads can induce signal transduction by directly transmitting forces from the extracellular matrix (ECM) to integrins, the cytoskeleton, and the nucleus, eventually resulting in changes in gene transcription and protein translation. Also, mechanical stretching of cells opens stretching-activated channels (SACs), causing influx of ions (e.g., Ca+) and thus a series of downstream signaling events. Still, mechanical loads acting on a cell may unfold a domain of the extracellular protein (M) and expose a cryptic site that may serve as an activating ligand for a cell surface receptor, which results in a series of signaling events. Additionally, mechanical load applied to a “force receptor” (FR) may initiate signal transduction, which results in transcription, followed by translation. As a result, soluble factors are secreted into the ECM which act on the receptor (R) and then initiate a cascade of signaling events. Other signaling molecules that are involved in mechanotransduction can include CD44 transmembrane protein and its intracellular domain (CD44ICD), which is translocated into the nucleus causing gene transcription.
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