Heparin and glomerular epithelial cell-secreted heparin-like species inhibit mesangial-cell proliferation

The regulation of cell growth in the kidney glomerulus plays a key role in many physiologic and pathologic processes. In this communication, the authors examine the possible role of heparin-like species as inhibitors of mesangial-cell proliferation. Heparin profoundly inhibited the growth of cultured mesangial cells in a dose-dependent manner, with an ED50 = 5-10 micrograms/ml. The antiproliferative activity of heparin was reversible and specific for mesangial cells as the target cell in the glomerulus. Heparin was much more effective than other glycosaminoglycans. Cultured glomerular epithelial cells were found to secrete both stimulators and inhibitors of mesangial-cell growth. Approximately half of the inhibitory activity was destroyed by a highly purified heparinase; the other half was sensitive to trypsin. Approximately 80% of the mitogenic activity was protease-sensitive. These results suggest that heparin and glomerular epithelial cells may participate in mesangial-cell growth regulation.