Production of an inhibitor of rat mesangial cell growth by the glomerulus and its alteration in puromycin nephrosis.
Mesangial cell proliferation is found in many forms of progressive renal disease. This proliferation may be due to dysregulation of mesangial cell growth. The studies presented here test the hypothesis that the normal glomerulus produces a regulator of mesangial cell growth. Conditioned media (CM) from primary glomerular cultures were able to inhibit rat mesangial cell growth in a dose- and time-dependent fashion, from 30.0 +/- 3.8 to 86.6 +/- 3.9% growth inhibition. The growth inhibitor in glomerular CM appears to have a molecular weight of less than 3,000. Glomerular CM caused significantly more growth inhibition than did 3T3 fibroblast CM, 77.9 +/- 2.8% growth inhibition by 10% glomerular CM versus 21.2 +/- 5.4% by 10% 3T3 CM (P < 0.001). The growth inhibition was completely reversible. Glomerular CM had no effect on the growth of 3T3 fibroblasts. Treatment of the glomerular CM with either trypsin or neutral protease had no effect on its growth inhibitory activity. Glomerular CM obtained from rats with puromycin aminonucleoside nephrosis caused significantly less growth inhibition than did control glomerular CM; at a concentration of 10% CM, control glomerular CM had 65.1 +/- 1.9% growth inhibition and puromycin had 45.4 +/- 2.1% (P < 0.001). Thus, the rat glomerulus produces a small, nonprotein inhibitor of rat mesangial cell growth and the activity of this inhibitor is reduced in puromycin nephrosis. Impairment of mesangial cell growth regulation may be important in the pathogenesis of progressive renal disease.
Groggel
G C
GC
Department of Medicine, University of Vermont, Burlington 05405.
Hughes
M L
ML
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D006497:Heparan Sulfate / Q000502:physiology; D007678:Kidney Glomerulus / Q000378:metabolism*; D051379:Mice; D008970:Molecular Weight; D009401:Nephrosis / Q000139:chemically induced* / Q000378:metabolism; D009928:Organ Specificity; D011691:Puromycin / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D017077:Culture Media, Conditioned; D006131:Growth Inhibitors; D006497:Heparan Sulfate; D011691:Puromycin