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Extracellular signal-regulated kinases and AP-1 mediate the up-regulation of vascular endothelial growth factor by PDGF in human vascular smooth muscle cells.
Int J Oncol. 2006 Jan; 28(1):135-41.IJ

Abstract

Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) have been shown to communicate with each other via cytokine signaling during neovascularization. In this study, we investigated the effect of platelet-derived growth factor (PDGF), a cytokine released from tumors and ECs, on vascular endothelial growth factor (VEGF) expression in human VSMCs and underlying signal transduction pathways. PDGF induced VEGF expression in a time- and concentration-dependent manner. PDGF induced the activation of extra-cellular signal-regulated kinase-1/2 (ERK-1/2), but not the activation of c-jun amino terminal kinase (JNK) and P38 mitogen-activated protein kinase (MAPK). Specific inhibitor of mitogen-activated protein kinase kinase (MEK)-1 was found to suppress VEGF expression and promoter activity. The expression of vectors encoding a mutated-type MEK-1 decreased the VEGF promoter activity. Electrophoretic mobility shift assay revealed that PDGF dose-dependently increased the DNA binding activity of AP-1. Transient transfection studies using an AP-1 decoy oligonucleotide confirmed that the activation of AP-1 is involved in PDGF-induced VEGF upregulation. Conditioned media from the human VSMCs pretreated with PDGF could remarkably stimulate the in vitro growth of human umbilical vein endothelial cells and this effect was partially abrogated by VEGF neutralizing antibodies. The above results suggest that ERK-1/2 and AP-1 signaling pathways are involved in the PDGF-induced VEGF expression in human VSMCs and that these paracrine signaling pathways induce endothelial cell proliferation.

Authors+Show Affiliations

Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, Kwangju 501-190, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16327989

Citation

Chang, Hee J., et al. "Extracellular Signal-regulated Kinases and AP-1 Mediate the Up-regulation of Vascular Endothelial Growth Factor By PDGF in Human Vascular Smooth Muscle Cells." International Journal of Oncology, vol. 28, no. 1, 2006, pp. 135-41.
Chang HJ, Park JS, Kim MH, et al. Extracellular signal-regulated kinases and AP-1 mediate the up-regulation of vascular endothelial growth factor by PDGF in human vascular smooth muscle cells. Int J Oncol. 2006;28(1):135-41.
Chang, H. J., Park, J. S., Kim, M. H., Hong, M. H., Kim, K. M., Kim, S. M., Shin, B. A., Ahn, B. W., & Jung, Y. D. (2006). Extracellular signal-regulated kinases and AP-1 mediate the up-regulation of vascular endothelial growth factor by PDGF in human vascular smooth muscle cells. International Journal of Oncology, 28(1), 135-41.
Chang HJ, et al. Extracellular Signal-regulated Kinases and AP-1 Mediate the Up-regulation of Vascular Endothelial Growth Factor By PDGF in Human Vascular Smooth Muscle Cells. Int J Oncol. 2006;28(1):135-41. PubMed PMID: 16327989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular signal-regulated kinases and AP-1 mediate the up-regulation of vascular endothelial growth factor by PDGF in human vascular smooth muscle cells. AU - Chang,Hee J, AU - Park,Jung S, AU - Kim,Mi H, AU - Hong,Min H, AU - Kim,Ki M, AU - Kim,Seok M, AU - Shin,Boo A, AU - Ahn,Bong W, AU - Jung,Young D, PY - 2005/12/6/pubmed PY - 2006/1/26/medline PY - 2005/12/6/entrez SP - 135 EP - 41 JF - International journal of oncology JO - Int J Oncol VL - 28 IS - 1 N2 - Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) have been shown to communicate with each other via cytokine signaling during neovascularization. In this study, we investigated the effect of platelet-derived growth factor (PDGF), a cytokine released from tumors and ECs, on vascular endothelial growth factor (VEGF) expression in human VSMCs and underlying signal transduction pathways. PDGF induced VEGF expression in a time- and concentration-dependent manner. PDGF induced the activation of extra-cellular signal-regulated kinase-1/2 (ERK-1/2), but not the activation of c-jun amino terminal kinase (JNK) and P38 mitogen-activated protein kinase (MAPK). Specific inhibitor of mitogen-activated protein kinase kinase (MEK)-1 was found to suppress VEGF expression and promoter activity. The expression of vectors encoding a mutated-type MEK-1 decreased the VEGF promoter activity. Electrophoretic mobility shift assay revealed that PDGF dose-dependently increased the DNA binding activity of AP-1. Transient transfection studies using an AP-1 decoy oligonucleotide confirmed that the activation of AP-1 is involved in PDGF-induced VEGF upregulation. Conditioned media from the human VSMCs pretreated with PDGF could remarkably stimulate the in vitro growth of human umbilical vein endothelial cells and this effect was partially abrogated by VEGF neutralizing antibodies. The above results suggest that ERK-1/2 and AP-1 signaling pathways are involved in the PDGF-induced VEGF expression in human VSMCs and that these paracrine signaling pathways induce endothelial cell proliferation. SN - 1019-6439 UR - https://www.unboundmedicine.com/medline/citation/16327989/Extracellular_signal_regulated_kinases_and_AP_1_mediate_the_up_regulation_of_vascular_endothelial_growth_factor_by_PDGF_in_human_vascular_smooth_muscle_cells_ L2 - https://www.spandidos-publications.com/ijo/28/1/135 DB - PRIME DP - Unbound Medicine ER -