90 - Inhibition of P2X7 receptor delays the progression of diabetic nephropathy and represses klotho expression

Abstract

Introduction Previous studies in our laboratory have suggested that P2X7 could contribute to the progression of diabetic nephropathy and modulate klotho expression. Aim of this study was to investigate the role of P2X7 knockdown in the onset of diabetic nephropathy and its possible relationship with klotho, in rats. Methods Seven-week-old male Wistar rats weighing 210g were all uninephrectomized; two-thirds were induced to diabetes with 60mg/kg streptozotocin i.v., and one-third received its vehicle (control rats). At 4th day of the fifth week of the protocol, half of the diabetic rats received a small interfering RNA targeting for P2X7 mRNA, and the other half received its vehicle. Euthanasia was made at the eighth week. Results Diabetic animals reproduced all classic symptoms of the disease; besides, they showed reduced renal function and low NO bioavailability; also, SOD1, SOD2 and catalase were increased, probably due to the oxidative stress factors which were elevated in this situation. Metabolic data of diabetic rats did not change by silencing P2X7 receptor. For the other hand, silencing P2X7 was able to increase plasma and membrane forms of klotho, which in turn could have contributed to balance oxidative and nitrosative profile, ultimately improving the renal function. Conclusion These findings suggest that the management of P2X7 receptor can benefit the kidneys or perhaps even other organs involved in diabetic nephropathy. It can be used as an adjuvant therapy in this disease, improving the quality of life of diabetic patients.