sphingosine-1-phosphate and Cell-Transformation--Viral

Connective tissue growth factor (CTGF) is induced by transforming growth factor-beta (TGF-beta) via Smad activation in mesangial cells. We recently reported that sphingosine 1-phosphate (S1P) induces CTGF expression in rat cultured mesangial cells. However, the mechanism by which S1P induces CTGF expression is unknown. The present study revealed that S1P-induced CTGF expression is mediated via pertussis toxin-insensitive pathways, which are involved in the activation of small GTPases of the Rho family and protein kinase C. We also showed by luciferase reporter assays and chromatin immunoprecipitation that S1P induces CTGF expression via Smad activation as TGF-beta does.

Topics: Animals; Blotting, Western; Cell Line, Transformed; Cell Transformation, Viral; Chromatin Immunoprecipitation; Connective Tissue Growth Factor; Genes, Reporter; Genetic Vectors; Glomerular Mesangium; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Luciferases; Lysophospholipids; MicroRNAs; Rats; Reverse Transcriptase Polymerase Chain Reaction; rho GTP-Binding Proteins; Sphingosine; Transcription, Genetic; Transfection