Endothelin and the glomerulus in chronic kidney disease. Semin Nephrol 2015 Mar;35(2):156-67
Date
05/13/2015Pubmed ID
25966347Pubmed Central ID
PMC4731878DOI
10.1016/j.semnephrol.2015.02.005Scopus ID
2-s2.0-84929045385 (requires institutional sign-in at Scopus site) 48 CitationsAbstract
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.
Author List
Barton M, Sorokin AAuthor
Andrey Sorokin PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
EndothelinsGlomerular Basement Membrane
Glomerular Filtration Rate
Humans
Renal Insufficiency, Chronic
