The MAPK-dependent regulation of the Jagged/Notch gene expression by VEGF, bFGF or PPAR gamma mediated angiogenesis in HUVEC

J Physiol Pharmacol. 2010 Apr;61(2):217-25.

Abstract

The Jagged-Notch signalling, plays a crucial role in cell differentiation. Angiogenesis, is regulated by VEGF, bFGF as well as by the free fatty acid metabolites , which are regulators of transcription factors such as peroxisome proliferation activating receptors (PPARs). The study analyzed the signalling pathways involved in the regulation of Jagged-1/Notch-4 expression in endothelial cells (HUVECs) in response to VEGF, bFGF and PPAR-gamma exogenous activator - ciglitazone. HUVECs were incubated with investigated substances for 24 hours, with or without the presence of the MAP-kinases inhibitors were used. Jagged-1 and Notch-4 gene expression was determined using quantitative Real-Time PCR. The Jagged-1/Notch-4 protein expression was compared by flow cytometry, when the phosphorylation-dependent activation of kinases was estimated by Western-blot method. The opposite effect of VEGF, bFGF, or ciglitazone on the Jagged-1/Notch-4 expression on HUVEC was connected with the different activation of MAPKs. Ciglitazone, activated p38 MAPK pathway and simultaneously inhibited phosphorylation of p42/44 MAPK. The pro-angiogenic: bFGF and VEGF, also activated the p38 MAPK, but they did not attenuate the p42/44 MAPK phosphorylation. Maintaining of the Jagged/Notch interactions by VEGF, when down-regulation by bFGF and ciglitazone, seems to be dependent on the different effect on p38 MAPK and p42/44 MAPK pathway regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Calcium-Binding Proteins / genetics*
  • Cells, Cultured
  • Fibroblast Growth Factor 2 / administration & dosage
  • Fibroblast Growth Factor 2 / metabolism
  • Flow Cytometry
  • Gene Expression Regulation*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Jagged-1 Protein
  • Membrane Proteins / genetics*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neovascularization, Physiologic / physiology*
  • PPAR gamma / administration & dosage
  • PPAR gamma / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Receptor, Notch4
  • Receptors, Notch / genetics*
  • Serrate-Jagged Proteins
  • Signal Transduction
  • Thiazolidinediones / pharmacology
  • Umbilical Veins / metabolism
  • Vascular Endothelial Growth Factor A / administration & dosage
  • Vascular Endothelial Growth Factor A / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • NOTCH4 protein, human
  • PPAR gamma
  • Proto-Oncogene Proteins
  • Receptor, Notch4
  • Receptors, Notch
  • Serrate-Jagged Proteins
  • Thiazolidinediones
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • ciglitazone