抄録
Sphingosine–1–phosphate (S1P) regulates cell migration, proliferation and apoptosis in vascular smooth muscle cells (VSMCs) and endothelial cells through the Edg family of multiple G protein–coupled receptor isoforms. The major source of S1P is activated platelets, suggesting its role in vascular remodeling. We previously demonstrated that S1P stimulated PDGF_B chain mRNA expression in newborn VSMCs ,but not in adult VSMCs, through the mechanisms mainly involving Gi–Ras–ERK. In this study we investigated which S1P receptor subtype is involved in S1P–induced PDGF_B chain mRNA expression in VSMCs. Newborn and adult VSMCs expressed comparable levels of S1P2 and S1P3 mRNAs. However, the expression levels of S1P1 mRNA were quite different : it was abundant in newborn RASM, whereas it was barely detectable in adult VSMCs. We found in adult VSMCs that overexpression of S1P1, but not S1P2, induced a robust S1P stimulation of PDGF–B chain mRNA. To test more directly the possibility that S1P1 mediates S1P stimulation of PDGF_B chain expression, we down–regulated the expression of S1P1 mRNA by RNA interference. Treatment of the newborn VSMCs with the siRNA specifically targeting S1P1, but not scrambled RNA duplex, effectively reduced S1P1 mRNA level and markedly inhibited S1P–induced expression of PDGF–B chain. These observations indicate that S1P1 mediates S1P upregulation of PDGF–B chain. [Jpn J Physiol 54 Suppl:S106 (2004)]
