Archives of Dermatological Research

, Volume 303, Issue 1, pp 41–47

PPARδ agonists suppress angiogenesis in a VEGFR2-dependent manner

  • Markus Meissner
  • Igor Hrgovic
  • Monika Doll
  • Roland Kaufmann
Original Paper

DOI: 10.1007/s00403-010-1091-y

Cite this article as:
Meissner, M., Hrgovic, I., Doll, M. et al. Arch Dermatol Res (2011) 303: 41. doi:10.1007/s00403-010-1091-y
  • 195 Downloads

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that have a pleiotropic impact on the regulation of differentiation, cell growth, and the metabolism of lipids and glucose. PPARδ agonists display a variety of effects on pro- and anti-tumor processes, and seem to have pro-angiogenic activity at very low concentrations. We analyzed the influence of higher concentrations of PPARδ agonists on angiogenesis and its underlying mechanisms. We found that treatment with PPARδ agonists inhibited the formation of capillary-like structures and endothelial cell migration. Since signaling via the vascular endothelial growth factor receptor-2 (VEGFR2) pathway is critical for angiogenic responses during chronic inflammation and tumor development, we explored whether PPARδ agonist inhibition acted by diminishing VEGFR2 expression. PPARδ agonists inhibited endothelial VEGFR2 protein expression in a time- and concentration-dependent manner. In contrast, neither tie-2, neuropilin-1 nor VEGFR1 expression was significantly affected by PPARδ agonist treatment. We also demonstrated that PPARδ agonists significantly suppressed accumulation of VEGFR2 mRNA. Consistent with these results, promoter luciferase assays showed that the inhibitory effects of PPAR agonists occur through suppression of VEGFR2 promoter activity. Hence, VEGFR-2 expression may be a critical molecular target of PPAR δ agonists, which may be responsible for their anti-angiogenic effects. These results may help to define the optimal therapeutic doses of PPARδ agonists in prospective therapeutic applications.

Keywords

PPAR delta mRNA VEGFR2 Angiogenesis 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Markus Meissner
    • 1
    • 2
  • Igor Hrgovic
    • 1
  • Monika Doll
    • 1
  • Roland Kaufmann
    • 1
  1. 1.Department of DermatologyJohann Wolfgang Goethe-UniversityFrankfurt am MainGermany
  2. 2.Department of Dermatology, Venerology and AllergologyUniversity of FrankfurtFrankfurt am MainGermany

Personalised recommendations