Integrin β1: A Mechanosignaling Sensor Essential for Connective Tissue Deposition by Fibroblasts

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.

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.

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.

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.