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

被引:57
作者
Herman, WH
Emancipator, SN
Rhoten, RLP
Simonson, MS
机构
[1] Case Western Reserve Univ, Sch Med, Dept Med, Div Nephrol, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA
[3] Univ Hosp Cleveland, Cleveland, OH 44106 USA
[4] Cleveland Clin Fdn, Dept Neurosurg, Cleveland, OH 44195 USA
关键词
vasoactive peptides; G protein-coupled receptors; renal hemodynamics;
D O I
10.1152/ajprenal.1998.275.1.F8
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 pi. Cultured human mesangial cells have both ET(A) and ET(B) 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.
引用
收藏
页码:F8 / F17
页数:10
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