title: Sphingosine 1-phosphate stimulates rat mesangial cell proliferation from outside the cells.
abstract: BACKGROUND
  Proliferation of mesangial cells (MCs) is the initial step in glomerulonephritis, and platelet-derived mediators have been shown to play a significant role in this proliferation. Sphingosine 1-phosphate (S1P), one of the sphingolipids, is abundantly stored in platelets and is released upon stimulation. We examined the effects of S1P and related sphingolipids on the cell fate of cultured MCs in order to elucidate potential roles of these lipid mediators in glomerulonephritis.
  
  
  METHODS
  Cell proliferation was evaluated by bromodeoxy uridine (BrdU) incorporation together with MTS assay. Apoptosis of MCs was evaluated by examining annexin V staining and typical morphological changes in nuclei. We also examined the metabolism of [(3)H]sphingosine in MCs in either the presence or absence of platelet-derived growth factor (PDGF). The expression of endothelial differentiation genes (edg), which are the cell surface receptors for S1P in MCs, was examined by RT-PCR.
  
  
  RESULTS
  S1P, but not the other sphingolipids, stimulated MC proliferation. In contrast, dimethylsphingosine (DMS) induced apoptosis in the MCs. The amount of sphingosine (Sph) converted into S1P was small and was not affected by PDGF. This observation suggested that Sph kinase activity producing S1P from Sph was low in the MCs. Furthermore, expression of edg-1, -2 and -5 in MCs was confirmed by RT-PCR.
  
  
  CONCLUSIONS
  Our observations suggest that S1P stimulates MC proliferation from outside the cells, and not as a second messenger for PDGF. The modulation of MC fate with sphingolipids may provide possible strategies for the treatment of glomerulonephritis.
authors.affiliation: Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Hanafusa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Koei
authors.initials: K
authors.lastname: Yamada
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hori
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Okuda
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D008246:Lysophospholipids; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D004247:DNA; C061800:N,N-dimethylsphingosine; D013110:Sphingosine