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Review
. 2013 May;2(4):160-166.
doi: 10.1089/wound.2012.0365.

Integrin β 1: A Mechanosignaling Sensor Essential for Connective Tissue Deposition by Fibroblasts

Andrew Leask  1
Affiliations
Review

Integrin β 1: A Mechanosignaling Sensor Essential for Connective Tissue Deposition by Fibroblasts

Andrew Leask. Adv Wound Care (New Rochelle). 2013 May.

Abstract

Significance: There is no effective drug treatment for fibrosis (i.e., pathological scarring). Identifying the fundamental mechanisms responsible for normal and pathological connective tissue deposition is likely to yield novel insights into how to control fibrotic conditions.

Recent advances: An increasing body of evidence suggests a link between mechanical tension and the development of scar tissue. Integrins are the cell surface receptors that mediate interactions between the cell and the surrounding extracellular matrix (ECM). Recent evidence has suggested that, in fibroblasts, the integrin β1-subunit plays an essential role in mechanosignaling and in dermal homeostasis, repair, and fibrosis. The mechanism underlying these activities of integrin β1 appears to involve its ability to (1) mediate activation of latent transforming growth factor beta-1 via ECM contraction and (2) modulate collagen production via a focal adhesion kinase/rac1/nicotinamide adenine dinucleotide phosphate oxidase (NOX)/reactive oxygen species (ROS) pathway. Moreover, the integrin β1-binding protein CCN2, a secreted matricellular protein located within the cellular microenvironment, is required for dermal fibrogenesis.

Critical issues: Mechanical tension is a key feature underlying the development of scar tissue. The mechanosignaling sensor integrin β1 is an essential, central mediator of dermal fibrosis, wound healing, and homeostasis.

Future directions: Drugs targeting the molecular mechanism underlying integrin β1-mediated signaling may represent a novel therapeutic approach for treating fibroproliferative disorders. Clinical trials directly testing this hypothesis are warranted.

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Figures

None
Andrew Leask, BSc, PhD
Figure 1.
Figure 1.
Mechancosignaling pathways mediating dermal connective tissue homeostasis, repair, and fibrosis. In differentiating myofibroblasts, ECM contraction via FA mediated by α-SMA results in the liberation of active TGFβ from LAP. In fibroblasts, integrin β1 contributes to basal collagen and α-SMA expression via a ROS-dependent mechanism. α-SMA, alpha–smooth muscle actin; ECM, extracellular matrix; FA, focal adhesion; FAK, focal adhesion kinase; LAP, latency-associated peptide; NOX, nicotinamide adenine dinucleotide phosphate oxidase; ROS, reactive oxygen species; TGF-β, transforming growth factor beta.
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