Figure 3
From: How does endothelial cell injury start? The role of endothelin in systemic sclerosis
Overview of ET-1 biosynthesis and function. Endothelial cell stimulation promotes the synthesis of pre-pro endothelin (ET)-1 polypeptides, the activation of processes that result in production of ET-1, and local release of mature ET-1. ET-1 interacts with specific endothelin receptors (endothelin receptor subtype A [ETA] and ETB) expressed on the surface of vascular smooth muscle cells and adventitial fibroblasts, and with ETB receptors in endothelial cells. Recognition of ET-1 by these receptors activates intracellular signalling pathways and cascades that result in rapid alterations in cell activity and function, and initiates transcriptional programmes. Several points along the pathways of production, release, receptor ligation and signalling, as well as transcriptional activation, are potential targets for intervention. aa, amino acids; ERA, endothelin receptor antagonist; IL, interleukin; siRNA, small interfering RNA; SMC, smooth muscle cell; TGF, transforming growth factor.