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Abstract: FR-PO405

Inhibition of P2X7 Receptor Delays the Progression of Diabetic Nephropathy and Represses Klotho Expression

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Higa, Elisa Mieko Suemitsu, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
  • Fernandes, Maria jose Da silva, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
  • Serralha, Robson Souza, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
  • Lima, Deyse, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
  • Punaro, Giovana, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
  • Rodrigues, Adelson, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

Group or Team Name

  • Laboratory of Nitric Oxide and Oxidative Stress
Background

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. Maneuvers like silencing P2X7 can be used as an adjuvant therapy in diabetes mellitus, improving the quality of life of these patients.