Vascular and glomerular expression of endothelin-1 in normal human
kidney.
Herman, William H., Steven N. Emancipator, R. L. Patrick Rhoten, and
Michael S. Simonson.
Department of Medicine, Division of Nephrology, and Department of
Pathology, School of Medicine, Case Western Reserve University and
University Hospitals of Cleveland, Cleveland, Ohio 44106. Department
of Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio,
44195
APStracts 5:0058F, 1998.
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 b1, 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 transforming growth factor b1, 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.
Received 19 August 1997; accepted in final form 25 February 1998.
APS Manuscript Number F271-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 9 March 1998