Synthesis of sulfated proteoglycans by bovine glomerular endothelial cells in culture.
It has been suggested that proteinuria is caused by alterations of the charge selectivity of the basement membrane and/or the epithelial cell layer (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. Therefore, we wanted to investigate the effects on endothelial GAG synthesis during normal and pathological conditions. We treated glomerular endothelial cell cultures with puromycin aminonucleoside (PAN, a nephrosis-inducing agent) or interleukin-1beta (IL-1beta) for a total of 72 h and compared the metabolic turnover and incorporation of [(35)S]sulfate during the last 2 days. In control cultures, the GAG content in the media supernatants increased 66 +/- 6% (mean +/- SE) between 12 and 42 h of incubation with radioactivity (P < 0.01, n = 8). The content of (35)S-labeled GAGs in the media was reduced by 31 +/- 1% by PAN (P < 0.001, n = 8) and increased by 141 +/- 15% by 10 U/ml IL-1beta (P < 0.01, n = 8). Treatment with enzymes revealed a dominance of heparan, chondroitin, and dermatan sulfate GAGs. Thus the glomerular endothelial cell production of GAGs was increased by IL-1beta and reduced by PAN. Therefore, it is conceivable that certain nephrotic conditions may be due to endothelial dysfunction, rather than other renal causes.
Sörensson
Jenny
J
Department of Nephrology, Göteborg University, SE-405 30 Göteborg, Sweden. jenny.sorensson@kidney.med.gu.se
Björnson
Anna
A
Ohlson
Maria
M
Ballermann
Barbara J
BJ
Haraldsson
Börje
B
D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000096:biosynthesis; D003871:Dermatan Sulfate / Q000096:biosynthesis; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004798:Enzymes / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006493:Heparin / Q000031:analogs & derivatives* / Q000378:metabolism; D006497:Heparan Sulfate / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011509:Proteoglycans / Q000096:biosynthesis* / Q000378:metabolism; D011692:Puromycin Aminonucleoside / Q000494:pharmacology
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004798:Enzymes; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D007375:Interleukin-1; D011509:Proteoglycans; D011692:Puromycin Aminonucleoside; C036090:heparin proteoglycan