Startseite Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
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Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration

  • Alexander Koch EMAIL logo , Manuel Jäger , Anja Völzke , Georgios Grammatikos , Dagmar Meyer zu Heringdorf , Andrea Huwiler und Josef Pfeilschifter
Veröffentlicht/Copyright: 19. Februar 2015

Abstract

Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1–5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.


Corresponding author: Alexander Koch, pharmazentrum frankfurt/ZAFES, Goethe University Hospital, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany, e-mail:

Acknowledgments

We gratefully acknowledge Juliane Dreke, Daniel Staudenraus, and Anna-Maria Grau (all pharmazentrum frankfurt/ZAFES) for excellent technical assistance. This work was supported by the German Research Foundation (KO3940/1-1, PF361/7-2, SFB1039, SPP1267/2), the Alfons und Gertrud Kassel-Stiftung (to A.K.), and the Swiss National Science Foundation (310030, 135619).

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Received: 2014-12-1
Accepted: 2015-2-11
Published Online: 2015-2-19
Published in Print: 2015-6-1

©2015 by De Gruyter

Artikel in diesem Heft

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: Molecular Medicine of Sphingolipids
  4. HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
  5. The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
  6. Sphingolipids in viral infection
  7. Tackling the biophysical properties of sphingolipids to decipher their biological roles
  8. Ceramide and sphingosine in pulmonary infections
  9. Molecular mechanisms of erythrocyte aging
  10. Sphingolipids in liver injury, repair and regeneration
  11. Ultrasound-stimulated microbubble enhancement of radiation response
  12. Innate immune responses in the brain of sphingolipid lysosomal storage diseases
  13. Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
  14. The role of sphingolipids in endothelial barrier function
  15. The effect of altered sphingolipid acyl chain length on various disease models
  16. Secretory sphingomyelinase in health and disease
  17. Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
  18. Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
  19. The molecular medicine of acid ceramidase
  20. Caenorhabditis elegans as a model to study sphingolipid signaling
  21. S1PR4 is required for plasmacytoid dendritic cell differentiation
  22. Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
  23. Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
  24. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
  25. Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
  26. Obituary
  27. The life and work of Dr. Robert Bittman (1942–2014)
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