Effect of Prostaglandin E₂ 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 human and experimental glomerulopathy, including that seen in diabetes. The nonsulfated glycosaminoglycan hyaluronan participates in the regulation of pericellular matrix assembly and is a mitogen in some cell types. We have shown previously that hyaluronan production is increased in the glomerulus in a glucose- and prostaglandin-dependent manner. We have investigated the effect of diabetes and of addition of hyaluronan and prostaglandin E₂ (PGE₂) on the uptake of [³H]thymidine by glomerular core preparations enriched in mesangial cells. When compared with nondiabetic controls, it was shown that [³H]thymidine uptake was significantly increased in glomerular core preparations from streptozotocin-induced diabetic rats (to 169 ± 5%, P < 0.001). In glomerular cores from both experimental groups, hyaluronan (50–250 ng/ml) or PGE₂ (10⁻¹² to 10⁻⁸ mol/l) increased the uptake of [³H]thymidine. Further, mesangial cells from nondiabetic control glomerular cores, when maintained in culture in early passage, responded with increased [³H]thymidine uptake to raised glucose (5.6–25 mmol/l) and to added hyaluronan and PGE₂. We propose that prostaglandin and hyaluronan production in response to a raised glucose environment in diabetes can contribute to mesangial hypercellularity.