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Updated: Oct 10, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
Signal transduction pathways involved in cytokine stimulation of endothelin-1 release from human vascular smooth
M Woods1, E G Wood, J A Mitchell
1Department of Cardiac, Vascular and Inflammation Research, St. Bartholomew's Hospital and the Royal London School of Medicine and Dentistry, London, UK.
Abstract:
Endothelin-1 (ET-1) mRNA expression and peptide production in human vascular smooth muscle cells (HVSMCs) are markedly increased by exposure to cytokines. As the transcription factor nuclear factor-kappaB (NF-kappaB) often mediates the effects of cytokines in target cells the aim of this study was to determine whether the production of ET-1 following exposure of HVSMCs to cytokines depends upon activation of NF-kappaB. BAY 11-7082, an inhibitor of cytokine-induced inhibitor protein (IkappaB) phosphorylation, inhibited cytokine-stimulated upregulation of preproendothelin-1 mRNA expression and ET-1 peptide production. In addition, immunoblotting showed that cytokine stimulation of ET-1 release in VSMCs involves nuclear translocation of NF-kappaB. In conclusion, NF-kappaB activation is involved in the stimulation by cytokines of ET-1 release from HVSMCs. As upregulated production of ET-1 within VSMCs may underlie the causative role of ET-1 in a number of disease states this finding indicates that NF-kappaB within HVSMCs could be central to a number of vascular pathologies.
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