Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing lung disease with a dismal
prognosis and a largely unknown etiology. Autotaxin (ATX) is a secreted lysophospholipase
D, largely responsible for extracellular production of lysophosphatidic acid (LPA),
a bioactive phospholipid. LPA has numerous effects in most cell types, signaling through
at least 6 receptors (LPAR) exhibiting wide spread distribution and overlapping specificities.
The ATX/LPA axis has been suggested as a therapeutic target in different chronic inflammatory
and fibroproliferative disorders, including pulmonary fibrosis. In this report, we
examined head-to-head the efficacy of a potent inhibitor of ATX (PF-8380), that has
not been tested in pulmonary fibrosis models, and an antagonist of LPAR1 (AM095) in
bleomycin (BLM)-induced pulmonary fibrosis. Both compounds abrogated the development
of pulmonary fibrosis and prevented the distortion of lung architecture, exhibiting
qualitative and quantitative differences in different manifestations of the modeled
disease.
