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Am J Physiol Renal Physiol 258: F259-F265, 1990;
0363-6127/90 $5.00
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AJP - Renal Physiology, Vol 258, Issue 2 259-F265, Copyright © 1990 by American Physiological Society

ARTICLES

Inhibition of rat mesangial cell growth by heparan sulfate

G. C. Groggel, G. N. Marinides, P. Hovingh, E. Hammond and A. Linker
Department of Medicine, University of Utah, School of Medicine, Salt Lake City.

The ability of heparan sulfate, an endogenous component of the glomerulus, to regulate the growth of cultured rat mesangial cells was investigated. Heparan sulfate caused a dose-dependent inhibition of rat mesangial cell growth, 85% inhibition compared with controls at the highest dose (1,000 micrograms/ml). Chondroitin sulfate produced no inhibition. The low-sulfated fraction of heparan sulfate (9%) produced more inhibition than the high-sulfated fraction (13%), 90 +/- 1 vs. 71 +/- 2% (P = 0.002). The effects of the heparan sulfate were completely reversible. Treatment of heparan sulfate with heparitinase increased the degree of inhibition, 71 +/- 1 vs. 84 +/- 1% (P less than 0.001). Four different oligosaccharides derived from heparan sulfate and heparin were tested for their ability to inhibit growth. One of the oligosaccharides, low-sulfated (10%), caused significant inhibition, 76 +/- 2%. Heparan sulfate was also able to inhibit the growth of Swiss 3T3 fibroblasts (63 +/- 5%). This inhibition was less marked than that seen with mesangial cells. Thus heparan sulfate was able to significantly inhibit rat mesangial cell growth in culture. Alterations in glomerular heparan sulfate may play an important role in alterations in mesangial cell growth.


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