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Articles in PresS, published online ahead of print October 8, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00257.2002
Submitted on July 17, 2002
Accepted on October 3, 2002
1 Department of Nephrology, Goteborg University, Goteborg, Sweden; Department of Medicine, Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY, USA
2 Department of Nephrology, Goteborg University, Goteborg, Sweden
3 Department of Medicine, Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY, USA
* To whom correspondence should be addressed. E-mail: jsoren{at}aecom.yu.edu.
It has previously been suggested that proteinuria is caused by alterations of the charge selectivity of the basement membrane and/or the epithelial cell layer (the podocytes). However, recent findings suggest that the endothelial luminal surface coat, consisting of proteoglycans with their connected glycosaminoglycan (GAG) branches and glycoproteins, may contribute to the permselectivity. We therefore wanted to investigate the effects on endothelial GAG synthesis during normal and pathological conditions. We treated glomerular endothelial cell cultures with either puromycin aminonucleoside (PAN - a nephrosis inducing agent) or IL-1ß for a total of 72 hours and compared the metabolic turnover and incorporation of [35S]-sulfate during the last two days. In control cultures, the glycosaminoglycan content in the media supernatants increased with 66 ±6% (mean ± SEM) between 12 to 42 hours of incubation with radioactivity (p<0.01, n = 8). PAN reduced the content of [35S]-glycosaminoglycans in the media with 31 ±1% (p<0.001, n = 8), while IL-1ß (10 U/ml) increased the concentration with 141 ±15% (p<0.01, n = 8). Treatment with enzymes revealed a dominance of heparin, chondroitin and dermatan sulfate GAGs. Thus, the glomerular endothelial cells production of glycosaminoglycans was increased by IL-1ß and reduced by PAN. It is therefore conceivable, that certain nephrotic conditions may be due to endothelial dysfunction rather than having other renal causes.
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