In contrast to S1PR2 blockade, the functional antagonism of S1PR1 by continuous administration of an S1PR1 agonist, which brought about robust S1PR1 internalization and consequent downregulation of cell surface S1PR1 in the vascular endothelium, led to aggravation of lung fibrosis due to impaired vascular barrier integrity [5,11]. This evidence concerns the gene S1PR2 and pulmonary fibrosis.