A modest proposal: targeting αv integrin-mediated activation of latent TGFbeta as a novel therapeutic approach to treat scleroderma fibrosis.

INTRODUCTION: The potent profibrotic cytokine transforming growth factor-β (TGF-β) has been associated with the onset and progression of the fibrosis seen in the autoimmune connective tissue disease scleroderma (systemic sclerosis, SSc).

AREA COVERED: This review explores the data supporting the notion that TGF-β contributes to SSc fibrosis and examines why initiating clinical trials in SSc aimed at targeting integrin-mediated latent TGF-β activation is timely.

EXPERT OPINION: Targeting TGF-β directly has not been proven to be clinically effective in this disease. Conversely, targeting matrix stiffness, which perpetuates fibrosis, may have more promise. Intriguingly, targeting integrin-mediated activation of latent TGF-β, which bridges these concepts, may have therapeutic value.