s-1743 and Cicatrix

Thyroid eye disease (TED) can lead to scar formation and tissue remodeling in the orbital space. In severe cases, the scarring process leads to sight-threatening pathophysiology. There is no known effective way to prevent scar formation in TED patients, or to reverse scarring once it occurs. In this study, we show that the proton pump inhibitors (PPIs), esomeprazole and lansoprazole, can prevent transforming growth factor beta (TGFβ)-mediated differentiation of TED orbital fibroblasts to myofibroblasts, a critical step in scar formation. Both PPIs prevent TGFβ-induced increases in alpha-smooth muscle actin (αSMA), calponin, and collagen production and reduce TED orbital fibroblast cell proliferation and migration. Esomeprazole and lansoprazole exert these effects through an aryl hydrocarbon receptor (AHR)-dependent pathway that includes reducing β-catenin/Wnt signaling. We conclude that PPIs are potentially useful therapies for preventing or treating TED by reducing the myofibroblast accumulation that occurs in the disease.

Topics: Actins; Calcium-Binding Proteins; Calponins; Cell Differentiation; Cells, Cultured; Cicatrix; Collagen; Esomeprazole; Fibroblasts; Graves Ophthalmopathy; HEK293 Cells; Humans; Lansoprazole; Microfilament Proteins; Myofibroblasts; Proton Pump Inhibitors; Receptors, Aryl Hydrocarbon; Transforming Growth Factor beta; Wnt Signaling Pathway