Autotaxin Is Highly Expressed in Systemic Sclerosis (SSc) Skin, Mediates Dermal Fibrosis Via IL-6, and Is a Target for SSc Therapy

Author: F. Castelino, L. George, G. Bain, L. Goulet, R. Lafyatis and A. Tager
Date Published: December-2014
Source: American College of Rheumatology

Autotaxin (ATX) is an enzyme present in biological fluids that is responsible for the production of the lipid mediator, lysophosphatidic acid (LPA). We previously implicated LPA and its receptor, LPA1 in SSc pathogenesis.1 Here we studied the role of ATX in SSc dermal fibrosis using the bleomycin (BLM) mouse model and skin biopsy samples from SSc patients and healthy controls. We evaluated the role of IL-6, a cytokine implicated in SSc, in mediating ATX-induced fibrosis. Additionally, we investigated the therapeutic potential of targeting ATX, by using a novel ATX inhibitor, PAT-048 in this model.