Netrin-1 May Promote Lung Fibrosis in Scleroderma Save

Mechanisms underlying the pulmonary fibrosis of systemic sclerosis are poorly understood, yet are the focus of both research and new drug development. 

Fibrocytes biology was studied, specifically looking at how extracellular matrix (ECM) in lung regulates collagen-producing fibrocyte-like cells in cultured human peripheral blood mononuclear cells (PBMCs). Decellularized lung explants from control subjects and PSS patients with ILD where used to create tissue scaffolds that could be studied. 

They found that scaffolds from PSS-ILD patients showed abnormal anatomy, stiffness, and abnormal ECM composition compared to controls. Researchers found that PBMCs from PSS-ILD patients showed increased responsiveness to components of decellularized fibrotic lungs. They found netrin-1 expression was increased in cells from PSS-ILD patients, and that depletion of netrin-1 improved fibrosis in a mice model.

Their findings factors in systemic sclerosis lung ECM regulate fibrocyte accumulation via a netrin-1-dependent pathway, thereby making netrin-1 a potential therapeutic target for systemic sclerosis-related ILD.