S1PR1 and pulmonary fibrosis: These results indicated that, different from TGF-β1, S1PR agonists activate PI3K/Akt and ERK1/2 signals, but not Smad2/3 signals, to mediate ECM synthesis, that is, S1PR agonists stimulate human pulmonary fibrosis by stimulating S1P1 and S1P2 in a Smad independent pathway (Sobel et al., 2013).