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Am J Physiol Renal Physiol 275: F8-F17, 1998;
0363-6127/98 $5.00
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Vol. 275, Issue 1, F8-F17, July 1998

Vascular and glomerular expression of endothelin-1 in normal human kidney

William H. Herman1, Steven N. Emancipator2, R. L. Patrick Rhoten3, and Michael S. Simonson1

1 Department of Medicine, Division of Nephrology, and 2 Department of Pathology, School of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland 44106; and 3 Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio 44195

To understand better the function of endothelin-1 (ET-1) in renal physiology, we examined vascular and glomerular expression of ET-1 in normal human kidney and in lupus nephritis. Immunohistochemical analysis revealed that renal endothelium of glomeruli, arteries, veins, and capillaries expressed ET-1. Endothelial cells were the principal source of glomerular ET-1; positive immunostaining was detected only rarely in mesangial cells and vascular smooth muscle cells from normal kidney. However, mesangial staining for ET-1 was elevated in patients with lupus nephritis, suggesting that under certain conditions mesangial cells elaborate ET-1. Indeed cultured human mesangial cells from normal subjects secreted ET-1 peptide. ET-1 secretion was augmented by the protein kinase C activator phorbol ester and by transforming growth factor-beta 1 (TGF-beta 1), a cytokine implicated in the development of glomerulosclerosis. Transient transfection of cultured mesangial cells with a preproET-1 reporter construct showed that the preproET-1 promoter is transcriptionally active in mesangial cells and is stimulated by TGF-beta 1, phorbol ester, or ectopic expression of protein kinase beta 1. Cultured human mesangial cells have both ETA and ETB receptors that contribute to ET-1-stimulated mitogenesis. Taken together, these results demonstrate that ET-1 is expressed at sites where paracrine or autocrine signaling by ET-1 might control renal vasoconstriction, glomerular filtration rate, and remodeling of the glomerulus in renal disease.

vasoactive peptides; G protein-coupled receptors; renal hemodynamics


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