Transcriptional regulation of connective tissue growth factor by sphingosine 1-phosphate in rat cultured mesangial cells

FEBS Lett. 2005 May 9;579(12):2576-82. doi: 10.1016/j.febslet.2005.03.073. Epub 2005 Apr 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Transformed
  • Cell Transformation, Viral
  • Chromatin Immunoprecipitation
  • Connective Tissue Growth Factor
  • Genes, Reporter
  • Genetic Vectors
  • Glomerular Mesangium / cytology*
  • Glomerular Mesangium / drug effects*
  • Immediate-Early Proteins / drug effects*
  • Intercellular Signaling Peptides and Proteins
  • Luciferases
  • Lysophospholipids / pharmacology*
  • MicroRNAs / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology*
  • Transcription, Genetic*
  • Transfection
  • rho GTP-Binding Proteins / metabolism


  • CCN2 protein, rat
  • Immediate-Early Proteins
  • Intercellular Signaling Peptides and Proteins
  • Lysophospholipids
  • MicroRNAs
  • Connective Tissue Growth Factor
  • sphingosine 1-phosphate
  • Luciferases
  • rho GTP-Binding Proteins
  • Sphingosine