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2015 ; 35
(2
): 156-67
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Endothelin and the glomerulus in chronic kidney disease
#MMPMID25966347
Barton M
; Sorokin A
Semin Nephrol
2015[Mar]; 35
(2
): 156-67
PMID25966347
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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.
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