Effects of endothelin-1 on thymidine uptake and fibronectin production of diabetic glomeruli

Endothelin-1 (ET-1) is a potent mitogenic and vasoconstricting agent. The effect of ET-1 upon the diabetic kidney may be important because diabetic glomeruli exhibit a poor contractile response and because diabetic kidneys do not contract even by end-stage renal failure.

In the present study, we investigated the effect of ET-1 on diabetic glomeruli that were freshly isolated from Wistar rats after streptozotocin-induced diabetes for 1 week (DM1W), 1 month (DM1M) and 3 months (DM3M), respectively, and then observed the glomerular uptake of [(3)H]-labelled thymidine and the production of fibronectin.

We found that the basal [(3)H]-labelled thymidine uptake of isolated glomeruli was significantly higher in DM1M and DM3M than in the normal control (both P < 0.05). ET-1 enhanced the [(3)H]-labelled thymidine uptake in both normal and DM1W glomeruli (both P < 0.005), but not in DM1M and DM3M, and all were not suppressed by exogenous medications. The basal production of fibronectin in isolated glomeruli was also significantly higher in DM1M and DM3M than in the normal controls (P < 0.05 and P < 0.005, respectively). ET-1 enhanced the fibronectin production in both normal and all diabetic groups. Pretreatment with insulin and dexamethasone suppressed the ET-1-enhanced fibronectin production in diabetic but not in normal glomeruli, while indomethacin and heparin had no effect in all groups.

Our results indicated that basal glomerular thymidine uptake and fibronectin production were enhanced in diabetic rats, and that ET-1 further enhanced the cellular proliferation and fibronectin production of isolated diabetic glomeruli. The ET-1-enhanced fibronectin production can be partially attenuated by insulin and dexamethasone.