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

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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.
Original languageEnglish
JournalJournal of Physiology and Pharmacology
Issue number2
Pages (from-to)217-25
Number of pages8
Publication statusPublished - 2010

Bibliographical note

Keywords: Blotting, Western; Calcium-Binding Proteins; Cells, Cultured; Fibroblast Growth Factor 2; Flow Cytometry; Gene Expression Regulation; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neovascularization, Physiologic; PPAR gamma; Proto-Oncogene Proteins; Receptors, Notch; Signal Transduction; Thiazolidinediones; Umbilical Veins; Vascular Endothelial Growth Factor A; p38 Mitogen-Activated Protein Kinases

ID: 21404996