S1P promotes YAP1 nuclear translocation via ligation to S1PR2. hPASMCs were treated with control or S1PR2 siRNA (30 nM) for 72 h and then stimulated with S1P (1 µM, 24 h). (A–C) Immunofluorescence staining of total cellular and nuclear YAP1 in hPASMCs and quantification data demonstrating that SIPR2 knockdown inhibits S1P-induced YAP1 expression and nuclear translocation; (D) real-time PCR showing decreased S1PR2 gene expression; (E,F) representative Western blot images and β-actin-normalized quantification of protein demonstrate that S1PR2 protein levels were significantly silenced by siRNA; (G,H) immunofluorescence staining and quantification data showing that the S1PR2 inhibitor JTE-013 (10 µM, 1 h pretreatment) inhibits the S1P (1 µM, 24 h)-induced nuclear localization of YAP1. n = 3; * p < 0.05 versus siRNA or vehicle control; ** p < 0.05 versus siRNA control or versus S1P alone. Scalebar: 25 μm.