MATRIX MODULATES UPTAKE OF CALCIUM-OXALATE CRYSTALS AND CELL-GROWTH OF RENAL EPITHELIAL-CELLS

Handling of urinary crystals by renal epithelial and medullary interstitial cells may play an important role in the pathogenesis of renal stones and associated renal scarring. We examined the effects of calcium oxalate monohydrate (CaOM) crystals on the proliferative activity of renal tubular cells (opossum kidney) and renal medullary interstitial cells in culture. We also studied the impact of altered extracellular matrix on cell proliferation as well as on uptake of crystals by epithelial cells. Epithelial cells incubated with CaOM showed greater (p <0.05) growth when compared with untreated cells (control, 10.5 +/- 1.1 versus CaOM, 16.6 +/- 1.6 X 10(6) cells per dish). The CaOM crystal-cell interaction also enhanced proliferation of interstitial cells (at 48 hours, control, 3.3 +/- 0.2 versus CaOM, 4.2 +/- 0.1 x 10(6) cells per dish, p <0.02; at 72 hours, control, 3.6 +/- 0.3 versus 5.5 +/- 0.4 x 10(6) cells per dish, p <0.01). Collagen, a constituent of extracellular matrix, inhibited (p <0.01) proliferation of epithelial cells. Semiconfluent epithelial cells grown on collagen gels showed greater (p <0.01) uptake of (45)CaOM crystals when compared with uptake by cells grown on either uncoated (control) or albumin-coated plastic dishes (control, 979.9 +/- 51.1, albumin, 876.4 +/- 28.3, collagen gel, 1502.5 +/- 103.8 cpm per well). Epithelial cells grown to confluence on collagen gels also showed enhanced (p <0.05) uptake of (45)CaOM crystals. Reflectance microscopy as well as ultrastructural studies revealed intracellular localization of CaOM crystals. These results indicate that CaOM crystals stimulate the growth of both epithelial and interstitial cells. Enhanced growth of interstitial cells may also lead to increased synthesis of extracellular matrix. The latter may further modulate crystal uptake as well as cell growth of adjacent epithelial cells. These findings may be important in the development of nephrolithiasis and associated interstitial scarring.