However, in lung disorders such as bronchopulmonary dysplasia (BPD) [147], pulmonary arterial hypertension (PAH) [148], asthma [149], experimental models of PF [150], and IPF [151] circulating and lung tissue levels of S1P were significantly elevated compared to controls, and reducing S1P levels by genetic deletion of Sphk1 in mice or inhibition of SPHK1 by small molecule inhibitors conferred protection. This evidence concerns the gene MBTPS1 and pulmonary arterial hypertension.