ENDOTHELIN-1 MEDIATES ERYTHROPOIETIN-STIMULATED GLOMERULAR ENDOTHELIAL CELL-DEPENDENT PROLIFERATION OF MESANGIAL CELLS

These experiments were performed in an attempt to determine whether ch ronic stimulation of glomerular endothelial cells with recombinant hum an erythropoietin would alter mesangial cell proliferation. Glomerular endothelial cells in culture incubated with various concentrations of erythropoietin for up to 4 days exhibited dose-dependent endothelin-1 production. Moreover, the conditioned medium from erythropoietin-stim ulated glomerular endothelial cells enhanced [H-3]thymidine incorporat ion into mesangial cells. This enhancement was significantly attenuate d in the presence of a endothelin A receptor antagonist, BQ-123. These results suggest that endothelin-1 mediates erythropoietin-stimulated glomerular endothelial cell-dependent mesangial cell proliferation, re sulting in the progression of glomerulonephritis.