EFFECT OF PROSTAGLANDIN E(2) AND HYALURONAN ON MESANGIAL CELL-PROLIFERATION - A POTENTIAL CONTRIBUTION TO GLOMERULAR HYPERCELLULARITY IN DIABETES

Proliferation of mesangial cells is a feature of several forms of huma n and experimental glomerulopathy, including that seen in diabetes. Th e nonsulfated glycosaminoglycan hyaluronan participates in the regulat ion of pericellular matrix assembly and is a mitogen in some cell type s. We have shown previously that hyaluronan production is increased in the glomerulus in a glucose- and prostaglandin-dependent manner. We h ave investigated the effect of diabetes and of addition of hyaluronan and prostaglandin E(2) (PGE(2)) on the uptake of [H-3]thymidine by glo merular core preparations enriched in mesangial cells. When compared w ith nondiabetic controls, it was shown that [H-3]thymidine uptake was significantly increased in glomerular core preparations from streptozo tocin-induced diabetic rats (to 169 +/- 5%, P < 0.001). In glomerular cores from both experimental groups, hyaluronan , (10(-12) to 10(-8) m ol/l) increased the uptake of [H-3]thymidine. Further, mesangial cells from nondiabetic control glomerular cores, when maintained in culture in early passage, responded with increased [H-3]thymidine uptake to r aised glucose (5.6-25 mmol/l) and to added hyaluronan and PGE(2). We p ropose that prostaglandin and hyaluronan production in response to a r aised glucose environment in diabetes can contribute to mesangial hype rcellularity.