EDN1
Description
The EDN1 (endothelin 1) is a protein-coding gene located on chromosome 6.
Endothelin 1 (ET-1), also known as preproendothelin-1 (PPET1), is a potent vasoconstrictor peptide produced by vascular endothelial cells, as well as by cells in the heart (affecting contractility) and kidney (affecting sodium handling). The protein encoded by this gene – EDN1 – is proteolytically processed to release endothelin 1. Endothelin 1 is one of three isoforms of human endothelin. Preproendothelin is precursor of the peptide ET-1. Endothelial cells convert preproendothelin to proendothelin and subsequently to mature endothelin, which the cells release. Patients with salt-sensitive hypertension have higher plasma ET-1. Endothelin-1 receptor antagonists (Bosentan) are used in the treatment of pulmonary hypertension. Use of these antagonists prevents pulmonary arterial constriction and thus inhibits pulmonary hypertension. As of 2020, the role of endothelin-1 in affecting lipid metabolism and insulin resistance in obesity mechanisms was under clinical research.
Endothelin-1 acts as a ligand for G-protein coupled receptors EDNRA and EDNRB, triggering a cascade involving PTK2B, BCAR1, BCAR3, RAP1, and RHOA GTPases in glomerular mesangial cells. It also binds to the DEAR/FBXW7-AS1 receptor. Endothelin-1 promotes remodeling of the mesenteric arterial wall through activation of ROCK signaling, leading to the colocalization of NFATC3 with F-actin filaments. Subsequently, NFATC3 translocates to the nucleus and promotes the transcription of ACTA2, a marker for smooth muscle hypertrophy and differentiation.
EDN1 is also known as ARCND3, ET1, HDLCQ7, PPET1, QME.
