Effect of Misoprostol on Mesangial Cell Growth and Collagen Metabolism

Independent of etiology, progressive chronic renal failure is characterized by accumulation of mesangial matrix and collagenous materials leading to glomerular sclerosis and closure. Pharmacologic intervention aimed at ameliorating this process has significant potential for substantial clinical benefit. We, therefore, assessed the effect of misoprostol on glomerular mesangial cell growth and collagen metabolism. Studies were carried out using a rat glomerular mesangial cell line cloned in our laboratory. At the concentration tested (1 &mgr;M), neither misoprostol nor prostaglandin E(2) had any effect on glomerular mesangial cell proliferation. Misoprostol did not change the absolute synthesis rates for collagen or total protein when measured by (14)C-proline incorporation into protein-associated hydroxyproline and proline respectively. However, the amount of collagen extruded into the medium, as a percentage of protein synthesis, was decreased by 10% in misoprostol-treated cells (p = 0.042). In addition, collagen breakdown was 26% greater in misoprostol-treated cultures (p = 0.044). Misprosotol had no such effects on cell cultures subjected to mechanical stress applied as continuous stretch-relaxation cycles. These results indicate that misoprostol influences mesangial cell collagen metabolism by increasing the rate of endogenous breakdown and decreasing collagen export outside the cell. Misoprostol has no effect on mesangial cell proliferation.