CYCLOOXYGENASE-DERIVED METABOLITES OF 8,9-EPOXYEICOSATRIENOIC ACID ARE POTENT MITOGENS FOR CULTURED RAT GLOMERULAR MESANGIAL CELLS

The mitogenic effects of 11(R)-hydroxy-8, 9-epoxyeicosatrienoic acid (EET) enantiomers were investigated in cultured rat glomerular mesangial cells. Both 11(R)-hydroxylated 8(R), 9(S)- and 8(S), 9(R)-EET at 1 μM stimulated [3H]-thymidine incorporation to 300% and 280%, with 50% maximal effect occurring at 8x10-9 M and 1x10-8 M, respectively. Similar concentration- dependent effects were observed in stimulating induction of the immediate early gene, c-fos. Mitogenic activity of the 11(R)-hydroxylated enantiomers was not affected by prior downregulation of protein kinase C, suggesting involvement of protein kinase C-independent mechanisms. These findings suggest that either trans- or intracellular metabolism of 8, 9-EET by cyclooxygenase occurs during inflammatory glomerular diseases and that the resulting metabolites are involved in mesangial cell proliferation. © 1993 Academic Press, Inc.