title: Endothelin and the glomerulus in chronic kidney disease.
abstract: Endothelin-1 (ET-1) is a 21-amino acid peptide with mitogenic and powerful vasoconstricting properties. Under healthy conditions, ET-1 is expressed constitutively in all cells of the glomerulus and participates in homeostasis of glomerular structure and filtration function. Under disease conditions, increases in ET-1 are critically involved in initiating and maintaining glomerular inflammation, glomerular basement membrane hypertrophy, and injury of podocytes (visceral epithelial cells), thereby promoting proteinuria and glomerulosclerosis. Here, we review the role of ET-1 in the function of glomerular endothelial cells, visceral (podocytes) and parietal epithelial cells, mesangial cells, the glomerular basement membrane, stromal cells, inflammatory cells, and mesenchymal stem cells. We also discuss molecular mechanisms by which ET-1, predominantly through activation of the ETA receptor, contributes to injury to glomerular cells, and review preclinical and clinical evidence supporting its pathogenic role in glomerular injury in chronic renal disease. Finally, the therapeutic rationale for endothelin antagonists as a new class of antiproteinuric drugs is discussed.
authors.affiliation: Molecular Internal Medicine, University of Zurich, Zurich, Switzerland. Electronic address: barton@access.uzh.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Barton
authors.affiliation: Department of Medicine, Kidney Disease Center, Division of Nephrology, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Andrey
authors.initials: A
authors.lastname: Sorokin
mesh_terms: D016232:Endothelins / Q000378:metabolism*; D050533:Glomerular Basement Membrane / Q000378:metabolism* / Q000473:pathology; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology
chemical_list: D016232:Endothelins
keywords: ERA; FSGS; GFR; albuminuria; blood pressure; chronic kidney disease; endothelin; endothelin receptor antagonists; epithelial cell; glomerulus; mesangial cells; podocyte; proteinuria