Integrin signaling in fibrosis and scleroderma.

Integrins are a large family of heterodimeric transmembrane receptors for extracellular matrix proteins. As well as mediating cell attachment and the bulk of force transduction from the cytoskeleton, they convey signals from the extracellular matrix to the cell. alpha1beta1 and alpha2beta1 are the major collagen receptors in this family. a1beta1 provides negative feedback on collagen synthesis, whereas alpha2beta1 stimulates the synthesis of matrix metalloproteases. Each receptor modulates the signaling activity of the other to coordinate matrix synthesis and remodeling. Expression of both is reduced in scleroderma despite a paracrine environment which would be expected to upregulate them. Deficiencies in the integrins correlate with upregulated collagen synthesis and downregulated metalloprotease synthesis seen during the disease.