Signals and genes induced by angiogenic growth factors in comparison to inflammatory cytokines in endothelial cells.
The evaluation of signaling pathways leading to gene induction by VEGF-A and IL-1 in endothelial cells supports the importance of the NF-kappaB pathway for the IL-1-induced gene repertoire, whereas VEGF-A is a strong and preferential trigger of signals via PLC-gamma. This leads (i) via Ca(++) to the activation of calcineurin and NFAT and (ii) via PKC and the MEK/ERK MAPK pathway to the upregulation of EGR-1. Part of the VEGF-triggered gene induction depends on a cooperation of the transcription factors NFAT and EGR-1. Gene activation via PLC-gamma provides VEGF with the potency to induce a wide spectrum of genes including many also upregulated by IL-1. A gene upregulated by VEGF and IL-1 is the DSCR-1 gene, which encodes an inhibitor of calcineurin. DSCR1 is induced by NFAT or NF-kappaB and limits Ca(++) signaling in a negative feed-back loop. Similarly, NAB2, a corepressor of EGR-1, is induced by EGR-1 and limits EGR-1 effects. Adenoviral overexpression of DSCR1 or NAB2 inhibited part of VEGF-induced gene expression and reduced sprouting in angiogenesis models.
Schweighofer
Bernhard
B
Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria.
Schultes
Julia
J
Pomyje
Jirí
J
Hofer
Erhard
E
D042501:Angiogenic Proteins / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000502:physiology; D015398:Signal Transduction; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D042501:Angiogenic Proteins; D016207:Cytokines; D007375:Interleukin-1; D042461:Vascular Endothelial Growth Factor A