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

ABSTRACT

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.

KEYWORDS:

• Fibrosis
• mechanotransduction
• CCN2
• integrins
• scleroderma
• dermal fibrosis
• systemic sclerosis

Article highlights

• Elevated TGF-β expression is associated with the early, inflammatory, pre-fibrotic phase of scleroderma.

• Strategies targeting TGF-β ligand to treat SSc skin fibrosis have not been successful clinically.

• Strategies targeting integrin αv-mediated activation of latent TGF-β to treat SSc skin fibrosis may be warranted.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no direct funding from any source.